Methods and devices for diagnosing, monitoring, or treating medical conditions through an opening through an airway wall

ABSTRACT

Methods and devices for diagnosing, monitoring, and/or treating tissue through an opening or port through an airway wall are provided herein.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.13/107,720, filed on May 13, 2011, the content of which is incorporatedherein by reference in its entirety.

FIELD OF THE INVENTION

This application is directed to methods and devices for diagnosing,monitoring, and/or treating medical conditions or tissue through anopening, port or channel through an airway wall.

BACKGROUND

It was found that creation of collateral channels in COPD patientsallowed expired air to pass out of the lungs and decompressedhyper-inflated lungs. Such methods and devices for creating andmaintaining collateral channels are discussed in U.S. patent applicationSer. No. 09/633,651, filed on Aug. 7, 2000, now issued U.S. Pat. No.6,692,494; U.S. patent application Ser. No. 09/947,144 filed Sep. 4,2001, now issued U.S. Pat. No. 7,175,644, Ser. No. 09/946,706, filed onSep. 4, 2001, now issued U.S. Pat. No. 6,749,606, and Ser. No.09/947,126 filed on Sep. 4, 2014, now issued U.S. Pat. No. 6,712,812;U.S. Provisional Application No. 60/317,338 filed on Sep. 4, 2001; U.S.Provisional Application No. 60/334,642 filed on Nov. 29, 2001; U.S.Provisional Application No. 60/367,436 filed on Mar. 20, 2002; and U.S.Provisional Application No. 60/374,022 filed on Apr. 19, 2002 each ofwhich is incorporated by reference herein in its entirety.

SUMMARY

Various methods and devices for diagnosing, monitoring, and/or treatingmedical conditions through an extra-anatomic opening, port or channel orother opening through an airway wall are provided.

The creation of collateral channels or extra-anatomic openings mayprovide convenient access points to the lung parenchyma or other tissuefor delivery of substances, tools, or devices to diagnose, monitor, ortreat structures, tissue, tumors or diseased tissue that may residewithin the lung. The use of such openings allows for diagnosis,monitoring, or treatment in a minimally invasive manner and efficientlydelivering needed substances, tools, or devices to the desired area.

In certain variations, a method of accessing target tissue in a lung isprovided which includes locating a target site on an airway wall,wherein the target site is in a location that allows for creation of anopening leading to the target tissue and for advancement of an elongateinstrument through the opening to the target tissue.

In certain variations, a method of accessing target tissue in a lung mayinclude advancing an elongate instrument to a target site in an airwayof the lung; creating an opening through the airway wall at the targetsite, where the opening leads to the target tissue; and advancing theelongate instrument through the opening to the target tissue.

In certain variations, a method of navigating an elongate instrumentthrough an opening in an airway wall to target tissue in the lung mayinclude advancing an elongate instrument within an airway of the lung;advancing the elongate instrument through an opening in the airway wall;and providing an electromagnetic sensor or electromagnetic field toguide or track the elongate instrument.

In certain variations, a method of accessing target tissue in a lung,may include locating a target site on an airway wall, wherein the targetsite is in a location that allows for creation of an opening leading tothe target tissue and for advancement of an elongate instrument throughthe opening to the target tissue; and providing an electromagneticsensor or electromagnetic field to guide or track the elongateinstrument.

In certain variations, methods and devices for treating a lung areprovided. A method includes treating diseased lung tissue by identifyinga region in a lung having the disease lung tissue, selecting a targetsite at an airway wall, creating an extra-anatomic opening at the targetsite; and delivering a substance through the extra-anatomic opening totreat the diseased tissue. The diseased tissue may be present beyond thewall of the airway and in the parenchymal tissue of the lung.

In certain variations, a method may or may not include placement of animplant. For example, a substance or device may or may not be deliveredthrough the implant. Moreover, the conduit may be subsequently removedfrom the airway after the diseased tissue or other tissue issufficiently treated or accessed. A treatment may treat regions ofdestroyed tissue and trapped gasses by inducing a collapse of thetissue. Alternatively, or in combination, the treatment may be directedtowards tumors or other conditions of the lung.

In certain variations, the methods relating to identifying regions oftissue, selecting a target site, avoidance of blood vessels, andcreation of the extra-anatomic opening may rely on the teachingsdiscussed herein that are suited to creation of a collateral opening forreleasing trapped gasses.

In certain variations, a substance or device may be delivered using anycatheter capable of being deployed in the lungs. Alternatively, or incombination, the substance or devices may be delivered using the devicesdescribed below.

In certain variations, methods for identifying the areas of the diseasedtissue using the modes described herein or other modes that are suitedfor the particular medical condition in question are provided. Forexample, a site for treating a tumor may be located using such meansthat are well suited for tumor identification.

In certain variations, methods and devices for selecting sites andcreating openings are provided. In one variation, a method includesselecting a treatment site in an airway of the lung, creating a hole inan airway wall of the airway; and expanding the hole in the airway wall.Selecting the treatment site may include visual inspection of the siteor inspection for the presence or absence of a blood vessel underneaththe surface of the airway wall. Selection of the site may be performedor aided by non-invasive imaging. Such imaging may include visualinspection, x-ray, ultrasound, Doppler, acoustic, MRI, PET, and computedtomography (CT) scans. Furthermore, a substance may be administered intothe lungs to assist in the selection of the treatment site. For example,the substance may comprise a hyperpolarized gas, a thermochromatic dye,a regular dye, and/or a contrast agent.

In certain variations, the use of a less-traumatic holemaker forcreation of the channel (note that a channel includes a hole that iscreated and subsequently expanded) is provided. The less traumaticholemaker may include a piercing member (e.g., a needle, a cannula, ablade, a tube, a rod or other similar structure). The less traumaticholemaker may also include devices which minimize the collateral damageto tissue (e.g., low temperature RF devices, pulsating RF, lowtemperature laser, ultrasound, high pressure water, etc.)

In certain variations, devices and methods that prevent closure of thechannel such that air may flow through the channel and into the airwayare provided. Such channels may be made by a variety of methods asdiscussed in the patents incorporated by reference above. For example,the channel may be made via a surgical incision, a needle, a rotarycoring device, etc. Furthermore, the channel may be made by an energybased device, e.g., RF device, laser, etc. However, it has been notedthat use of low temperature devices, e.g., mechanical devices, to createthe channel result in less trauma to surrounding tissue and therebyminimize the healing response of the tissue. Accordingly, such modes ofcreating the channel often result in less occlusion of the channel.

In certain variations, a method may include expanding the hole byinserting a conduit into the hole. Furthermore, the method may comprisepartially expanding the hole by deploying the conduit in the hole, andthen fully expanding the hole by expanding the conduit within the hole.Preventing closure may be performed using various approaches including,but not limited to, biochemical, electrical, thermal, irradiation, ormechanical approaches (or any combination thereof).

In certain variations, delivering a bio-active composition, as describedherein, to maintain patency of the channel or conduit is provided. Thebio-active composition may be delivered to the airway wall prior tocreation of the channel, subsequent to creation of the channel, and/orafter insertion and deployment of the conduit. The bio-activecomposition may also be delivered through a drug eluting process, eitherthrough a composition placed on the conduit, or via delivery of aseparate eluting substance. Biochemical approaches include delivery ofmedicines that inhibit closure of the surgically created channel. Themedicines may be delivered locally or systematically. In one variation,a delivery catheter includes a dispense lumen that sends a drug to thetarget site. Also, bioactive substances may be delivered to the channeltissue using various delivery vehicles such as a conduit. The bioactivesubstance may be disposed on an exterior surface of the conduit suchthat it interacts with the channel tissue when the conduit is placed atthe injury site. Also, bioactive substances may be delivered to thechannel tissue before or after the conduit is positioned in the channel.The bioactive agent may also be delivered to the target site alone. Thatis, a medicine may be sent to the surgically created channel as the solemechanism for maintaining the patency of the channel. Also, systematicdelivery of medicines may be carried out through digestion, injection,inhalation, etc. Systematic delivery of medicines may be provided aloneor in combination with other techniques described herein. For example, apatient having undergone the procedures described herein may beprescribed steroids and/or COX-2 inhibitors in an attempt to prolong theeffects of the treatment.

In certain variations, any of the conduits discussed herein may alsoinclude at least one visualization feature disposed on a portion of thetissue barrier. The visualization feature may be a stripecircumferentially disposed about at least a portion of the centersection. The visualization feature serves to aid in placement ordeployment of the conduit in a target site.

In certain variations, a conduit for maintaining the patency of achannel created in tissue comprises a radially expandable center sectionand extension members as described above. A bioactive substance isdisposed on at least a portion of a surface of the conduit. Also, whenthe conduit is radially expanded it has an overall length and an innerdiameter such that a ratio of the overall length to the inner diameterranges from 1/6 to 2/1. The conduit may also be provided such that thisratio ranges from 1/4 to 1/1 and perhaps, 1/4 to 1/2. A tissue barriermay be disposed on at least a portion of the exterior surfacecorresponding to the center section. The tissue barrier may be comprisedof various materials including but not limited to polymers andelastomers. An example of a material which may be used for the tissuebarrier is silicone. Additional matrixes of biodegradable polymer andmedicines may be associated with the tissue barrier such that controlleddoses of medicines are delivered to the tissue opening.

In certain variations, a hole-making catheter for creating and dilatingan opening within tissue is provided. The catheter may include anelongate shaft having a proximal portion and a distal portion, and atleast one lumen extending through the proximal end; a balloon having aninterior in fluid communication with the lumen, the balloon located onthe distal portion of the elongate shaft, the balloon having anuninflated state and an inflated state; a piercing member located at thedistal portion of the elongate shaft, the piercing member beingextendable and retractable within the elongate shaft; and a depthlimiter stop located on the exterior of the distal portion of theelongate shaft, proximal to the balloon and larger in working diameterthan the uninflated balloon, which limits the maximum penetration of thecatheter into tissue.

The piercing member may include a body portion having a lumen extendingtherethrough. The lumen of the piercing member may be in fluidcommunication with a central lumen of the elongate shaft. In somevariations, an obturator is used within the device, where the obturatoris slidably located within the lumen of the elongate body and piercingmember.

The elongate body and/or piercing member may have multiple lumens. Forexample, they may be constructed from multi-lumen tubing. In somevariations, the piercing member is retractable within the elongateshaft.

The balloon member may consist of a distensible balloon or anon-distensible balloon. For either type of balloon, the workingdiameter may closely match the outer diameter of the piercing member.

In certain variations, an implant located about the balloon of thedevice is provided. In use, the piercing member would create a channelwithin the tissue, the device is then further advanced until the implantis located within the channel. Inflation of the balloon then deploys theimplant within the channel thereby improving the patency of the channel.Implants include, but are not limited to, a stent, conduit, grommet,valve, graft, anchor, etc.

In certain variations, the device may access airways deep within thelung. The elongate shaft may be comprised of a flexible material. Inparticular, the elongate shaft may be sufficiently flexible to passthrough a fully articulated bronchoscope.

In certain variations, a piercing member may also be used to deliverbio-active agents to the site of the collateral channel. As describedherein, such agents may increase the duration of patency of the channelsand/or implants.

In certain variations, a balloon catheter for deploying a device withinan opening in tissue is provided. The balloon catheter may include anelongate shaft having a proximal portion, a distal portion, a proximalend, a distal end; and at least one lumen extending through the proximalend, a balloon having an interior in fluid communication with the lumen,the balloon located on the distal end portion of the elongate shaft, aguide member extending distally from the distal end of the elongateshaft, the guide member comprising a rounded surface at an end oppositeto the elongate shaft, where the guide member has sufficient columnstrength to penetrate the opening in tissue, the guide member furthercomprising at least one resistance surface a such that when the bodyenters the opening, the resistance surface exerts resistance againsttissue upon removal of the guide member from the opening. The resistancesurface may have an increased diameter greater to provide resistanceupon removal from tissue. It may alternatively, or in combination,comprise a rough surface to provide added friction upon removal of thedevice. The guide member may be tapered, rounded, partially-spherical,elliptical, prolate, cone-shaped, triangular, or any similar shape. Itis contemplated that there may be more than one resistance surface onthe guide body. Moreover, the guide body may have a wavy/variablediameter shape providing several resistance surfaces on the areas ofincreased diameter. The device may also be used with an implant that maybe located about the balloon where upon expansion of the balloon, theimplant deploys. The implant may be selected from a stent, conduit,grommet, valve, graft, and anchor.

In another variation, the balloon catheter may further comprise adilating member located distally of the balloon. The dilating member maybe is located on the distal portion of the shaft between the distal endand the balloon and may comprise a tapered section, a second balloon, orother similar structure. In some variations, the dilating member may beretractable within the elongate shaft. The device may also include aneedle assembly moveably located in the instrument lumen, where theneedle assembly is advanceable through a hole-making lumen and out ofthe opening in the rounded surface.

In certain variations, the balloon catheter may be constructed to besufficient flexibility to advance through a fully articulatedbronchoscope. The balloon catheter may also be configured to deliverbio-active substances (e.g., drugs, medicines, compounds, etc.) to thetissue, either via the elongate tube or the guide member. Furthermore,the device may be adapted to provide suction to clear the target site.

In certain variations, a hole-making catheter for creating and dilatingan opening within tissue is provided. The catheter may include; anelongate shaft having a proximal portion and a distal portion, and atleast one lumen extending through the proximal end; a nondistensibleballoon having an interior in fluid communication with the lumen, thenondistensible balloon located on the distal portion of the elongateshaft; and a piercing member located at the distal portion of theelongate shaft, the piercing member being extendable and retractablewithin the elongate shaft.

In certain variations, an implant delivery system for deploying theimplant within a wall of tissue is provided. The system may include; anelongate shaft having a distal portion, a proximal end, a distal end, atleast one lumen extending through the proximal end; a balloon memberhaving an interior in fluid communication with the lumen, the balloonmember located on the distal portion of the elongate shaft; a piercingmember distally located to the distal end of the elongate shaft withinthe second lumen, the solid piercing member having a sharpened distalend adapted to penetrate tissue; and an expandable implant located aboutthe balloon member.

The preceding illustrations are examples of variation of the devices andmethods described therein. It is contemplated that, where possible,combinations of features/aspects of specific embodiments or combinationsof the specific embodiments themselves are within the scope of thisdisclosure.

This application is also related to the following applications60/420,440 filed Oct. 21, 2002; 60/387,163 filed Jun. 7, 2002; Ser. No.10/235,240 filed Sep. 4, 2002; Ser. No. 09/947,144 filed Sep. 4, 2001,now issued U.S. Pat. No. 7,175,644; Ser. No. 09/908,177 filed Jul. 18,2001, now abandoned; Ser. No. 09/633,651 filed Aug. 7, 2000, now issuedU.S. Pat. No. 6,692,494; and 60/176,141 filed Jan. 14, 2000; Ser. No.10/080,344 filed Feb. 21, 2002, now issued U.S. Pat. No. 7,422,563; Ser.No. 10/079,605 filed Feb. 21, 2002, now issued U.S. Pat. No. 7,022,088;Ser. No. 10/280,851 filed Oct. 25, 2002, now abandoned; and Ser. No.10/458,085 filed Jun. 9, 2003, now abandoned; and Ser. No. 11/538,950filed Oct. 5, 2006, now issued U.S. Pat. No. 8,409,167. Each of which isincorporated by reference herein in their entirety for all purposes.Applications: Ser. No. 10/458,085 filed Jun. 9, 2003, now abandoned;Ser. No. 10/951,962 filed Sep. 28, 2004, now abandoned; and Ser. No.11/335,263 filed Jan. 18, 2006, now issued U.S. Pat. No. 8,308,682 arealso incorporated by reference herein in their entirety for allpurposes.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A-1C illustrate various states of the natural airways and theblood-gas interface.

FIG. 1D illustrates a schematic of a lung demonstrating a principle ofthe inventions described herein.

FIG. 2A illustrates a side view of a conduit in an undeployed state.

FIG. 2B illustrates a side view of the conduit of FIG. 2A shown in adeployed shape.

FIG. 2C illustrates a front view of the conduit shown in FIG. 2B.

FIG. 2D is a cylindrical projection of the undeployed conduit shown inFIG. 2A.

FIG. 2E illustrates a side view of another variation of a conduit in anundeployed shape.

FIG. 2F illustrates a side view of the conduit of FIG. 2E in a deployedstate.

FIG. 2G is a cylindrical projection of the undeployed conduit shown inFIG. 2E.

FIG. 3A illustrates a side view of a conduit having a tissue barrier ina deployed state.

FIG. 3B illustrates a side view of a conduit having a tissue barrier.

FIG. 3C is a front view of the conduit shown in FIG. 3B.

FIG. 3D illustrates a conduit positioned in a channel created in atissue wall.

FIG. 3E is a cross sectional view of the conduit shown in FIG. 3B takenalong line 3E-3E.

FIGS. 3F-3G depict another conduit including a membrane that supports abioactive substance; the bioactive substance may be coated on themembrane.

FIGS. 4A-4C a variation of selecting a site, creating a channel at thesite using a less traumatic hole-maker, and expanding the channel.

FIGS. 4D-4K illustrate variations of piercing members for creatingcollateral channels.

FIGS. 5A-5C illustrate a method for deploying a conduit.

FIGS. 5D-5E illustrate a method for deploying a conduit within anotherimplant.

FIGS. 6A-6B illustrate a method for deploying a conduit at an angle.

FIGS. 7A-7B illustrate placement of a conduit within a channel by usinga guide member.

FIGS. 8A-8F illustrate additional variations of guide bodies for use acatheters

FIGS. 9A-9B illustrate additional features for use with guide bodies.

FIGS. 10A-10B respectively illustrate delivery of substances through anopening in the airway and through a conduit placed within the opening.

FIG. 11 illustrates a variation of a device for creating a supportstructure for an airway.

FIG. 12 illustrates another variation of a device for creating a supportstructure for an airway

FIG. 13 illustrates a variation of a device for creating a channel orpathway through an opening or port in an airway wall.

FIG. 14 illustrates a variation of a device for delivering instrumentsor tools through an opening or port in an airway wall.

FIG. 15 illustrates a variation of a clamp for collapsing tissue.

FIG. 16 illustrates method for reducing the volume of bullae in thelung, via an opening or port in an airway wall.

FIG. 17 illustrates a variation of a device and method for compressinghyperinflated segments of a lung.

FIGS. 18A-B illustrate variations of elastic members to be affixed totissue within a lung.

FIG. 19 illustrates a variation of a system or method utilizing multipleextra-anatomic openings or ports in an airway wall.

FIG. 20 illustrates a variation of a device and method for performingimaging.

FIG. 21 illustrates a variation of a device and method for performing anultrasound through an opening or port in an airway wall.

FIG. 22 illustrates one variation of a cutting catheter which may beadvanced through an opening or port through an airway wall for theremoval of various tissue.

FIG. 23 illustrates a variation of a catheter for delivering a sealant.

FIG. 24 illustrates a variation of a biopsy or tissue sampler.

FIGS. 25A-B illustrate variations of a method and a device forperforming a pleurocentesis.

FIG. 26 illustrates a variation of a pacing device which may be advancedthrough an opening or port through the airway wall.

DETAILED DESCRIPTION

Various methods and devices for diagnosing, monitoring, and/or treatingmedical conditions through an extra-anatomic opening, port or channel orother opening through an airway wall are described herein.

In certain variations, devices (and methods) for accessing or treatingvarious tissues, e.g., lung tissue, parenchyma or diseased lung tissue,are described herein. In certain variations, methods and devices aredescribed that serve to make or maintain collateral openings or channelsthrough an airway wall so that air is able to pass directly out of thelung tissue and into the airways or so that substances or devices may bedelivered to target tissue or lung tissue or parenchymal tissue beyondthe airways but within the lungs.

In certain variations, a channel, opening, extra-anatomic opening orport is meant to include, but not be limited to, any opening, hole,slit, channel or passage created in the tissue wall (e.g., airway wall).A channel may be created in tissue having a discrete wall thickness andthe channel may extend all the way through the wall. Also, a channel mayextend through lung tissue which does not have well defined boundariessuch as, for example, parenchymal tissue.

In certain variations, openings or channels may be maintained bypreventing or inhibiting tissue from growing into or otherwise blockingthe opening or channel. Chemical, electrical, light, mechanical, or acombination of any two or more of these approaches may be performed tomaintain the channel openings. For example, the channel walls may betreated with a bioactive agent which inhibits tissue growth. Thebioactive agent may be delivered locally or systematically. Also, thechannels may be treated with radiofrequency energy, heat, electricalenergy, or radiation to inhibit tissue overgrowth. These treatments maybe performed once, periodically, or in response to the severity of thechannel blockage. For example, the tissue blockage may be periodicallyremoved with a laser or another tissue-removal tool. Also, mechanicaldevices and instruments may be deployed in the channel to prevent tissuegrowth from blocking the channel. Mechanical devices include withoutlimitation conduits, valves, sponges, etc. These mechanical devices maybe deployed permanently or temporarily. If deployed temporarily, thedevices are preferably left in the channel for a sufficient amount oftime such that the channel tissue heals coaxially around the device ifthe medical practitioner intends to create a permanent opening in theairway wall.

FIGS. 1A-1C are simplified illustrations of various states of a naturalairway and a blood gas interface found at a distal end of those airways.FIG. 1A shows a natural airway 100 which eventually branches to a bloodgas interface 102.

Although not shown, the airway comprises an internal layer of epithelialpseudostratified columnar or cuboidal cells. Mucous secreting gobletcells are also found in this layer and cilia may be present on the freesurface of the epithelial lining of the upper respiratory airways.Supporting the epithelium is a loose fibrous, glandular, vascular laminapropria including mobile fibroblasts. Deep in this connective tissuelayer is supportive cartilage for the bronchi and smooth muscle for thebronchi and bronchioles.

FIG. 1B illustrates an airway 100 and blood gas interface 102 in anindividual having COPD. The obstructions 104 impair the passage of gasbetween the airways 100 and the interface 102. FIG. 1C illustrates aportion of an emphysematous lung where the blood gas interface 102expands due to the loss of the interface walls 106 which havedeteriorated due to a bio-chemical breakdown of the walls 106. Alsodepicted is a constriction 108 of the airway 100. It is generallyunderstood that there is usually a combination of the phenomena depictedin FIGS. 1A-1C. Often, the states of the lung depicted in FIGS. 1B and1C may be found in the same lung.

FIG. 1D illustrates airflow in a lung 118 when conduits 200 are placedin collateral channels 112. As shown, collateral channels 112 (locatedin an airway wall) place lung tissue 116 in fluid communication withairways 100 allowing air to pass directly out of the airways 100 whereasconstricted airways 108 may ordinarily prevent air from exiting the lungtissue 116. While the invention is not limited to the number ofcollateral channels which may be created, it is to be understood that 1or 2 channels may be placed per lobe of the lung and perhaps, 2-12channels per individual patient. However, as stated above, the inventionincludes the creation of any number of collateral channels in the lung.This number may vary on a case by case basis. For instance, in somecases in an emphysematous lung, it may be desirable to place 3 or morecollateral channels in one or more lobes of the lung.

Although FIG. 1D depicts a mechanical approach to maintaining channelsin the airway walls, the channel openings may be maintained using avariety of approaches or combinations of approaches.

As shown in FIGS. 2A-2G, the conduits described herein in certainvariations, generally include a center section 208 and at least oneextension member (or finger) 202 extending from each end of the centersection. The extension members, as will be discussed in more detailbelow, are capable of deflecting or outwardly bending to secure theconduit in an opening created in an airway wall thereby maintaining thepatency of the opening. The extension members may deflect such thatopposing extension members may form a V, U or other type of shape whenviewed from the side.

Additionally, the conduits shown in FIGS. 2A-2G include a center-controlsegment 235, 256 which restricts or limits radial expansion of thecenter section. The center-control segments are adapted to straighten asthe center section is radially expanded. Once the center-controlsegments become straight or nearly straight, radial expansion of theconduit is prevented. In this manner, the radial expansion of theconduit may be self controlled.

It is understood that the conduits discussed herein are not limited tothose shown in the figures. Instead, conduits of various configurationsmay be used as described herein. Such conduits are described in thefollowing U.S. patent application Ser. No. 09/908,177 filed Jul. 18,2001, now abandoned; International Application No. PCT/US03/12323 filedApr. 21, 2003; U.S. patent application Ser. No. 09/947,144 filed Sep. 4,2001, now issued U.S. Pat. No. 7,175,644; U.S. patent application Ser.No. 10/235,240 filed Sep. 4, 2002, now abandoned; and U.S. patentapplication Ser. No. 10/458,085 filed Jun. 9, 2003, now abandoned, theentirety of each of which is hereby incorporated by reference.

Conduit States

The conduits described herein may have various states (configurations orprofiles) including but not limited to (1.) an undeployed state and (2.)a deployed state.

The undeployed state is the configuration of the conduit when it is notsecured in an opening in an airway wall and, in particular, when itsextension members (or fingers) are not outwardly deflected to engage theairway wall. FIG. 2A is a side view of a conduit 200 in an undeployedstate. As shown in this figure, extension members 202A, 202B extendstraight from the ends 210, 212 respectively of center section 208. Theextension members shown in this example are parallel. However, theinvention is not so limited and the extension members need not beparallel.

The deployed state is the configuration of the conduit when it issecured in a channel created in an airway wall and, in particular, whenits extension members are outwardly bent to engage the airway wall suchthat the conduit is fixed in the opening. An example of a conduit in itsdeployed configuration is shown in FIGS. 2B and 2C. FIG. 2B is a sideview of a conduit in its deployed state and FIG. 2C shows a front viewof the conduit of FIG. 2B.

Center Section of the Conduit

As shown in FIGS. 2A-2D, the conduit includes a center section 208having a short passageway. This center section may be a tubular-shapedopen-frame (or mesh) structure having a plurality of ribs. Also, asexplained in more detail below, the center section may be a sheet ofmaterial.

The axial length of the center section or passageway may be relativelyshort. In FIGS. 2A-2D, the passageway's length is about equal to thewidth of a wire segment or rib. Here, the center section serves as abridge or junction for the extension members and it is not required tobe long. The axial length of the passageway may therefore be less than 1mm and even approach 0 mm. In one example, the length of the centersection is less than twice the square root of a cross sectional area ofthe center section. However, the center section may also havepassageways which have lengths greater than 1 mm.

The overall length (L) of the conduit may be distinguished from thelength of the center section because the overall length includes thelengths of the extension members. Further, the overall length (L) isdependent on which state the conduit is in. The overall length of theconduit will typically be shorter when it is in a deployed state asshown in FIG. 2B than when it is in an undeployed state as shown in FIG.2A. The overall length (L) for a deployed conduit may be less than 6 mmand perhaps, between 1 and 20 mm.

FIG. 2C shows a front view of the conduit 200 shown in FIG. 2B. FIG. 2Cshows the passageway having a hexagonal (or circular) cross section. Thecross-section, however, is not so limited. The cross section may becircular, oval, rectangular, elliptical, or any other multi-faceted orcurved shape. The inner diameter (D₁) of the center section, whendeployed, may range from 1 to 10 mm and perhaps, from 2 to 5 mm.Moreover, in some variations, the cross-sectional area of thepassageway, when deployed, may be between 0.2 mm² to 300 mm² and perhapsbetween 3 mm² and 20 mm²

The diameter of the center section, when deployed, thus may besignificantly larger than the passageway's axial length (e.g., a 3 mmdiameter and an axial length of less than 1 mm). This ratio of thecenter section length to diameter (D1) may range from about 0:10 to10:1, 0.1:6 to 2:1 and perhaps from 1:2 to 1:1.

The diameter of the center section, when deployed, may also be nearlyequal to the overall length (L) of the conduit 200. This overall length(L) to diameter (D1) ratio may range from 1:10 to 10:1, 1:6 to 2:1, andperhaps from 1:4 to 1:1. However, the invention is not limited to anyparticular dimensions or ratio unless so indicated in the appendedclaims. Rather, the conduit should have a center section such that itcan maintain the patency of a collateral channel in an airway wall. Thedimensions of the center section (and the conduit as a whole) may bechosen based on the tissue dimensions. When the channel is long in itsaxial length, for example, the length of the center section may likewisebe long or identical to the channel's length.

Extension Members of the Conduit

As mentioned above, extending from the ends of the center section 208are extension members 202A, 202B which, when the conduit is deployed,form angles A1, A2 with a central axis of the passageway. When viewedfrom the side such as in FIG. 2B, opposing extension members may have aV, U, or other shape. The extension members 202A, 202B may thusoutwardly rotate until they sandwich tissue (not shown) between opposingextension members.

The angles A1, A2 may vary and may range from, for example, 30 to 150degrees, 45 to 135 degrees and perhaps from 30 to 90 degrees. Opposingextension members may thus form angles A1 and A2 of less than 90 degreeswhen the conduit is deployed in a channel. For example, angles A1 and A2may range from 30 to 60 degrees when the conduit is deployed.

The conduits of the present invention are effective and may maintain asurgically created opening despite not substantially sandwiching tissuebetween opposing extension members as described above. Additionally, itis not necessary for the conduits of the present invention to preventair from flowing along the exterior of the conduit. That is, air maymove into (and through) spaces between the exterior of the conduit andthe interior wall of the tissue channel. Thus, fluidly sealing the edgesof the conduit to prevent side flow or leakage around the conduit is notcrucial for the conduits to be effective. However, the conduits of thepresent invention are not so limited and may reduce or eliminate sideflow by, for example, increasing the angles A1 and A2 and adding sealantaround the exterior of the conduit.

Moreover, the angle A1 may be different than angle A2. Accordingly, theconduit may include proximal extension members which are parallel (ornot parallel) to the distal extension members. Additionally, the anglecorresponding to each proximal extension member may be different oridentical to that of another proximal extension member. Likewise, theangle corresponding to each distal extension member may be different oridentical to that of another distal extension member.

The extension members may have a length between 1 and 20 mm and perhaps,between 2 and 6 mm. Also, with reference to FIG. 2C, the outer diameter(D₂) of a circle formed by the free ends of the extension members mayrange from 2 to 20 and perhaps, 3 to 10 mm. However, the invention isnot limited to the dimensions disclosed above. Furthermore, the lengthof the distal extension members may be different than the length of theproximal extension members. The length of the distal extension membersmay be, for example, longer than that of the proximal extension members.Also, the lengths of each proximal extension member may be different oridentical to that of the other proximal extension members. Likewise, thelengths of each distal extension member may be different or identical tothat of the other distal extension members.

The number of extension members on each end of the center section mayalso vary. The number of extension members on each end may range from2-10 and perhaps, 3-6. Also, the number of proximal extension membersmay differ from the number of distal extension members for a particularconduit. Moreover, the extension members may be symmetrical ornon-symmetrical about the center section. The proximal and distalextension members may also be arranged in an in-line pattern or analternating pattern. The extension members or the center section mayalso contain barbs or other similar configurations to increase adhesionbetween the conduit and the tissue. The extension members may also haveopenings to permit tissue ingrowth for improved retention.

The shape of the extension members may also vary. They may beopen-framed and somewhat petal-shaped as shown in FIGS. 2A-2D. In thesefigures, the extension members 202A, 202B comprise wire segments or ribsthat define openings or spaces between the members. However, theinvention is not so limited and the extension members may have othershapes. The extension members may, for example, be solid or they may befilled.

In another variation the conduit is constructed to have a deliverystate. The delivery state is the configuration of the conduit when it isbeing delivered through a working channel of a bronchoscope, endoscope,airway or other delivery tool. The maximum outer diameter of the conduitin its delivery state must therefore be such that it may fit within thedelivery tool, instrument, or airway.

In one variation, the conduit is radially expandable such that it may bedelivered in a smaller working channel of a scope while maximizing thediameter to which the conduit may expand upon deployment. For example,sizing a conduit for insertion into a bronchoscope having a 2 mm orlarger working channel may be desirable. Upon deployment, the conduitmay be expanded to have an increased internal diameter (e.g., 3 mm.)However, the invention is not limited to such dimensions. It iscontemplated that the conduits 200 may have center sections that areexpanded into a larger profile from a reduced profile, or, the centersections may be restrained in a reduced profile, and upon release of therestraint, return to an expanded profile.

Additionally, the conduit need not have a smaller delivery state. Invariations where the center section is not able to assume a secondsmaller delivery profile, a maximum diameter of the first or deployedprofile will be sufficiently small such that the conduit may be placedand advanced within an airway or a working channel of a bronchoscope orendoscope. Also, in cases where the conduit is self-expanding, thedeployed shape may be identical to the shape of the conduit when theconduit is at rest or when it is completely unrestrained.

Additionally the conduit may be partially expanded in its proximalregion in the delivery state, as shown in figure X. The partiallyexpanded portion would still me sized small enough to fit within theworking channel of the bronchoscope, but would be significantly larger(e.g., 0.5-2 mm) larger that the distal portion of the conduit. Thispartial expansion allows for easy placement of the conduit by providinga physical stop for the conduit within the airway wall. After theconduit is placed the entire conduit can be expanded to its intendedexpanded shape.

The partial expansion state can also be achieved by partially inflatingthe proximal section of the conduit with a separate balloon on thedelivery device. Another possible method is to design the conduit topreferentially expand the proximal section before the distal section,thereby partially expanding the conduit to create the size differential,placing the stent inside the airway wall with the aid of the stop, andthen fully expanding the conduit.

Control Members

The conduit 200 shown in FIGS. 2A-2D also includes diametric-controlsegments, tethers, or leashes 235 to control and limit the expansion ofthe center section 208 when deployed. This center-control segment 235typically is shaped such that when the conduit radially expands, thecenter-control segment bends until it is substantially straight or nolonger slack. Such a center-control segment 235 may be circular orannular shaped. However, its shape may vary widely and it may have, forexample, an arcuate, semi-circular, V, or other type of shape whichlimits the expansion of the conduit.

Typically, one end of the center-control segment is attached or joinedto the center section at one location (e.g., a first rib) and the otherend of the center-control segment is connected to the center section ata second location (e.g., a rib adjacent or opposite to the first rib).However, the center-control segments may have other constructs. Forexample, the center-control segments may connect adjacent ornon-adjacent center section members. Further, each center-controlsegment may connect one or more ribs together. The center-controlsegments may further be doubled up or reinforced with ancillary controlsegments to provide added control over the expansion of the centersection. The ancillary control segments may be different or identical tothe primary control segments.

FIG. 2B illustrates the conduit 200 in its deployed configuration. Asdiscussed above, the center-control segments 235 may bend or otherwisedeform until they maximize their length (i.e., become substantiallystraight) such as the center-control segments 235 shown in FIG. 2B.However, as discussed above, the invention is not so limited and othertypes of center-control segments may be employed.

As shown in FIGS. 2E-2G, control segments 252 may also be used to joinand limit the expansion of the extension members 254 or the controlsegments may be placed elsewhere on the conduit to limit movement ofcertain features to a maximum dimension. By controlling the length ofthe control segments, the shape of the deployed conduit may becontrolled. In the conduit shown in FIGS. 2E-2G, the conduit includesboth center-control segments 256 and distal control segments 252. Thecenter-control segments are arcuate shaped and join adjacent ribsections of the center section and the distal-control segments arearcuate and join adjacent distal extension members.

FIG. 2F illustrates the conduit in a deployed configuration and showsthe various control members straightening as the extension members andcenter section deploy. The proximal extension members, however, are notrestricted by a control member and consequently may be deflected to agreater degree than the distal extension members. Accordingly, a conduithaving control members connecting, for example, regions of the centersection and having additional control segments connecting extensionmembers, may precisely limit the maximum profile of a conduit when it isdeployed. This is desirable where overexpansion of the conduit ishazardous.

This also serves to control the deployed shape of the conduit by, forinstance, forcing angle A1 to differ from angle A2. Using controlsegments in this manner can provide for cone-shaped conduits if thevarious types of control-segments have different lengths. For example,providing longer proximal-control segments than distal-control segmentscan make angle A1 larger than angle A2. Additionally, cylindrical-shapedconduits may be provided if the center-control segments and theextension-control segments are sized similarly such that angle A1 equalsangle A2. Again, the control segments straighten as the conduit expandsand the conduit is thus prevented from expanding past a predeterminedamount.

The control segments, as with other components of the conduit, may beadded or mounted to the center section or alternatively, they may beintegral with the center section. That is, the control segments may bepart of the conduit rather than separately joined to the conduit withadhesives or welding, for example. The control segments may also bemounted exteriorly or interiorly to the members to be linked.Additionally, sections of the conduit may be removed to allow areas ofthe conduit to deform more readily. These weakened areas provide anotherapproach to control the final shape of the deployed conduit. Details forcreating and utilizing weakened sections to control the final shape ofthe deployed conduit may be found in U.S. patent application Ser. No.09/947,144 filed on Sep. 4, 2001, now issued U.S. Pat. No. 7,175,644.

Manufacture and Materials

The conduit described herein may be manufactured by a variety ofmanufacturing processes including but not limited to laser cutting,chemical etching, punching, stamping, etc. For example, the conduit maybe formed from a tube that is slit to form extension members and acenter section between the members. One variation of the conduit may beconstructed from a metal tube, such as stainless steel, 316L stainlesssteel, titanium, titanium alloy, nitinol, MP35N (anickel-cobalt-chromium-molybdenum alloy), etc. Also, the conduit may beformed from a rigid or elastomeric material that is formable into theconfigurations described herein. Also, the conduit may be formed from acylinder with the passageway being formed through the conduit. Theconduit may also be formed from a sheet of material in which a specificpattern is cut. The cut sheet may then be rolled and formed into a tube.The materials used for the conduit can be those described above as wellas a polymeric material, a biostable or implantable material, a materialwith rigid properties, a material with elastomeric properties, or acombination thereof. If the conduit is a polymeric elastic tube (e.g. athermoplastic elastomer), the conduit may be extruded and cut to size,injection molded, or otherwise formed.

Additionally, the conduits described herein may be comprised of a shapememory alloy, a super-elastic alloy (e.g., a NiTi alloy), a shape memorypolymer, or a shape memory composite material. The conduit may beconstructed to have a natural self-assuming deployed configuration, butis restrained in a pre-deployed configuration. As such, removal of therestraints (e.g., a sheath) causes the conduit to assume the deployedconfiguration. A conduit of this type could be, but is not limited tobeing, comprised from an elastic polymeric material, or shape memorymaterial such as a shape memory alloy. It is also contemplated that theconduit could comprise a shape memory alloy such that, upon reaching aparticular temperature (e.g., 98.5° F.), it assumes a deployedconfiguration.

Also, the conduit described herein may be formed of a plasticallydeformable material such that the conduit is expanded and plasticallydeforms into a deployed configuration. The conduit may be expanded intoits expanded state by a variety of devices such as, for example, aballoon catheter.

The conduit's surface may be modified to affect tissue growth oradhesion. For example, an implant may comprise a smooth surface finishin the range of 0.1 micrometer to 0.01 micrometer. Such a finish mayserve to prevent the conduit from being ejected or occluded by tissueovergrowth. On the other hand, the surface may be roughened or porous.The conduit may also comprise various coatings and tissue barriers asdiscussed below.

Tissue Barrier

FIG. 3A illustrates another variation of a conduit 200 having a tissuebarrier 240. The tissue barrier 240 prevents tissue ingrowth fromoccluding the collateral channel or passage of the conduit 200. Thetissue barrier 240 may coaxially cover the center section from one endto the other or it may only cover one or more regions of the conduit200. The tissue barrier may completely or partially cover the conduit solong as the ends are at least partially open. Moreover, the tissuebarrier may only be placed on the center section of the conduit. Thetissue barrier 240 may be located about an exterior of the conduit'ssurface, about an interior of the conduit's surface, or the tissuebarrier 240 may be located within openings in the wall of the conduit'ssurface. Furthermore, in some variations of the invention, the centersection 208 itself may provide an effective barrier to tissue ingrowth.The tissue barrier, of course, should not cover or block the entranceand exit of the passageway such that air is prevented from passingthrough the conduit's passageway. However, in some constructs, thetissue barrier may partially block the entrance or exit of thepassageway so long as air may continue to pass through the conduit'spassageway.

The tissue barrier may be formed from a material, mesh, sleeve, orcoating that is a polymer or an elastomer such as, for example,silicone, fluorosilicone, polyurethane, PET, PTFE, or expanded PTFE.Other biocompatible materials will work, such as a thin foil of metal,etc. The coatings may be applied, for example, by either dip coating,molding, spin-coating, transfer molding or liquid injection molding.Alternatively, the tissue barrier may be a tube of a material and thetube is placed either over and/or within the conduit. The tissue barriermay then be bonded, crimped, heated, melted, shrink fitted or fused tothe conduit. The tissue barrier may also be tied to the conduit with afilament of, for example, a suture material.

Still other techniques for attaching the tissue barrier include: solventswelling applications and extrusion processes; wrapping a sheet ofmaterial about the conduit, or placing a tube of the material about theconduit and securing the tube to the conduit. The tissue barrier may besecured on the interior of the conduit by positioning a sheet or tube ofmaterial on the inside of the center section and securing the materialtherein.

The tissue barrier may also be formed of a fine mesh with a porosity ortreatment such that tissue may not penetrate the pores. For example, aChronoFlex™ DACRON® or TEFLON® mesh having a pore size of 100-300microns may be saturated with collagen or another biocompatiblesubstance. This construct may form a suitable tissue barrier. The meshmay be coaxially attached to a frame such as the open frame structuresdisclosed above. Still other suitable frames include a continuous spiralmetallic or polymeric element. Given the mesh's radial strength or lackthereof, the use of a reinforcement element serves to prevent theimplant from collapsing. Also, as described below, other substances maybe applied to the exterior surface of the conduit to control elution ofvarious medicines.

FIGS. 3B and 3C respectively illustrate a side view and a front view ofanother conduit 300 having a partial tissue barrier coating. The conduit300 includes a center section 310, a plurality of extension members 320,and a partial tissue barrier 330. The conduit 300 is thus different thanthat shown in FIG. 3A in that the center section is longer and that thetissue barrier 330 only partially covers the extension members 320. Inparticular, the center section 310 shown in FIGS. 3B-3C is cylindricalor tubular-shaped. This shape may be advantageous when a relatively longpassageway is desired. Also, it is to be understood that the overall (orthree dimensional) shape of the center section, when deployed, is notlimited to the shape shown here. Rather, it may have various shapes suchas, for example, rectangular, tubular, conical, hour-glass,hemi-toroidal, etc.

Additionally, the tissue barrier 330 covers only a first region 350 ofthe extension members and leaves a second region 340 of the extensionmembers uncovered. The second or free region 340 of the extensionmembers 320 is shown as being open-framed. However, the invention is notso limited. The second region of the extension members may be solid andit may include indentations, grooves, and recesses for tissue ingrowth.Also, the extension members may include small holes for tissue ingrowth.For example, the second region of the extension members may have a densearray of small holes. In any event, the conduits described herein mayinclude at least one region or surface which is susceptible to tissueingrowth or is otherwise adherent to the tissue. Accordingly, tissueingrowth at the second region 340 of the extension members isfacilitated while tissue growth into the passageway 325 is thwarted.

As shown in FIG. 3D, tissue growth 360 into the uncovered region 340further secures the extension members to the tissue wall 370. Freeregion 340 of the extension members may also include tissue growthsubstances such as epithelial growth factors or agents to encouragetissue ingrowth. Accordingly, conduit 300 may be configured to engagethe tissue wall 370 as well as to allow tissue to grow intopredetermined regions of the conduit.

Visualization Feature

The conduit shown in FIG. 3A also includes a visualization ring ormarker 242. The marker 242 is visually apparent during a procedure. Themarker is observed as the conduit is placed in a collateral channel and,when the marker is even with the opening of the channel, the conduit maybe deployed. In this manner, the visualization feature facilitatesalignment and deployment of the conduits into collateral channels.

The visualization ring or mark may be a biocompatible polymer and have acolor such as white. Also, the visualization feature may protrude fromthe center section or it may be an indentation(s). The visualizationmark may also be a ring, groove or any other physical feature on theconduit. Moreover, the visualization feature may be continuous orcomprise discrete segments (e.g., dots or line segments).

The visualization feature may be made using a number of techniques. Inone example, the mark is a ring formed of silicone and is white. Thepolymeric ring may be spun onto the tissue barrier. For example, a clearsilicone barrier may be coated onto the conduit such that it coaxiallycovers the extension members and the center section as shown in FIG. 3A.Next, a thin ring of white material such as a metal oxide suspended inclear silicone may be spun onto the silicone coating. Finally, anothercoating of clear silicone may be applied to coat the white layer. Theconduit thus may include upwards of 1-3 layers including a tissuebarrier, a visualization mark layer, and a clear outer covering.

The shape of the visualization mark is not limited to a thin ring. Thevisualization mark may be large, for example, and cover an entire halfof the conduit as shown in FIG. 3B. The visualization mark may, forexample, be a white coating disposed on the proximal or distal half ofthe conduit. The visualization mark thus may extend from an end of theextension members to the center section of the conduit. As explained inmore detail below, when such a device is deposited into a channelcreated in lung tissue, the physician may observe when one-half of theconduit extends into the channel. This allows the physician to properlyactuate or deploy the conduit to secure the conduit in the tissue wall.

Accordingly, the visualization member is made visually apparent for usewith, for example, an endoscope. The visualization feature, however, mayalso be made of other vision-enhancing materials such as radio-opaquemetals used in x-ray detection. It is also contemplated that otherelements of the conduit can include visualization features such as butnot limited to the extension members, tissue barrier, control segments,etc.

In some variations of the invention, it was found that incorporation ofa bioactive, as discussed herein, or other substance into the coatingcaused a coloration effect in the composition layer (e.g., the polymerturns white). This coloration obscures the support member structure inthe layer making it difficult to identify the edges and center of thesupport member or implant. As discussed herein, placement of the implantmay depend upon positioning the center of the implant within the openingin tissue. If the support member structure is identifiable, then one isable to visually identify the center of the implant. When thecomposition colors obscures the support member or renders the implantotherwise opaque, it may become difficult to properly place the device.This may be especially true when the composition layer extendscontinuously over the support member.

Additionally, the coloration may render the visualization mark difficultto identify especially under direct visualization (e.g., using a scope).In some cases it was undesirable to simply add additional substances onor in the composition layer for marking because such substances couldpossibly interfere with the implant's ability to deliver the substanceas desired. To address these issues, a variation of the inventionincludes a delivery device for delivering an expandable implant (such asthose described herein and in the cases referenced herein), where thedelivery device includes an expandable member having an expandableimplant located about the expandable member. Where the implant and theexpandable member are of different visually identifiable colors orshades such that they distinction is easy to identify under endoscopicor bronchoscopic viewing.

In one example, as shown in FIG. 9C, a balloon catheter has a coloredsleeve 306 located about the balloon. The sleeve 306 comprises avisually identifiable color where selection of the colors should easeidentification of the implant an endoscopic visualization system (e.g.,blue or a similar color that is not naturally occurring within thebody.) The implant is placed about the sleeve 306 where the proximal anddistal areas of the implant would be identifiable by the difference incolor. Such a system allows a medical practitioner to place the implant200 properly by using the boundary of the implant 200 to guide placementin the tissue wall. The sleeve 306 may be fashioned from any expandablematerial, such as a polymer. Optionally, the sleeve 306 may also providean elastic force to return the balloon to a reduced profile afterexpansion of the balloon. Such a system allows for identificationwithout affecting the properties of the implant.

It should be noted that variations of the invention include coloring theballoon itself, or other expandable member, a color that meets the abovecriteria.

In another variation, the visualization mark may comprise providing acontrast between the implant and a delivery catheter. In one example theimplant is appears mostly white and while mounted on a contrasting colorinflation balloon. In this example the implant would be placed over ablue deflated balloon catheter. The proximal and distal areas of theimplant would be flanked by the deflated blue balloon, thus giving theappearance of a distinct distal and proximal end of the implant. Thiswould allow a physician to place the implant properly by using the blueflanks as a guide for placing the central white portion in the tissuewall. Similarly, a colored flexible sheath covering the balloon wouldalso suffice.

It is noted that while the visualization features described above aresuitable for use with the implants described herein, the inventivefeatures are not limited as such. The features may be incorporated intoany system where placement of an implant under direct visualizationrequires clear identification of the implant regardless of whether theimplant is opaque or colored.

Bioactive Agents

As discussed above, the bio-active substance or combination of bioactivesubstances is selected to assists in modifying the healing response as aresult of the trauma to the lung tissue resulting from creation of thecollateral channel. As noted above, the term lung tissue is intended toinclude the tissue lining the airway, the tissue beneath the lining, andthe tissue within the lung but exterior to the airway (e.g., lungparenchyma.) The purpose of modifying the healing response is to furtherextend the patency of the channel or implant to increase the durationwhich trapped gasses may exit through the implant into the airways. Theterm antiproliferative agent is intended to include those bioactivesubstances that directly modify the healing response described herein.

The bioactive substances are intended to interact with the tissue of thesurgically created channels and in particular, lung tissue. Thesesubstances may interact with the tissue in a number of ways. They may,for example, 1.) accelerate cell proliferation or wound healing toepithelialize or scar the walls of the surgically-created channel tomaintain its patent shape or 2.) the substances may inhibit or halttissue growth when a channel is surgically created through an airwaywall such that occlusion of the channel due to tissue overgrowth isprevented. Additionally, other bioactive agents may inhibit woundhealing such that the injury site (e.g., the channel or opening) doesnot heal leaving the injury site open and/or inhibit infection (e.g.,reduce bacteria) such that excessive wound healing does not occur whichmay lead to excessive tissue growth at the channel thereby blocking thepassageway.

A variety of bioactive substances may be used alone or in combinationwith the devices described herein. Examples of bioactive substancesinclude, but are not limited to, antimetabolites, antithrobotics,anticoagulants, antiplatelet agents, thorombolytics, antiproliferatives,antinflammatories, agents that inhibit hyperplasia and in particularrestenosis, smooth muscle cell inhibitors, growth factors, growth factorinhibitors, cell adhesion inhibitors, cell adhesion promoters and drugsthat may enhance the formation of healthy neointimal tissue, includingendothelial cell regeneration. The positive action may come frominhibiting particular cells (e.g., smooth muscle cells) or tissueformation (e.g., fibromuscular tissue) while encouraging different cellmigration (e.g., endothelium, epithelium) and tissue formation(neointimal tissue).

Still other bioactive agents include but are not limited to analgesics,anticonvulsives, anti-infectives (e.g., antibiotics, antimicrobials),antineoplastics, H2 antagonists (Histamine 2 antagonists), steroids,non-steroidal anti-inflammatories, hormones, immunomodulators, mast cellstabilizers, nucleoside analogues, respiratory agents,antihypertensives, antihistamines, ACE inhibitors, cell growth factors,nerve growth factors, anti-angiogenic agents or angiogenesis inhibitors(e.g., endostatins or angiostatins), tissue irritants (e.g., a compoundcomprising talc), poisons (e.g., arsenic), cytotoxic agents (e.g., acompound that can cause cell death), various metals (silver, aluminum,zinc, platinum, arsenic, etc.), epithelial growth factors or acombination of any of the agents disclosed herein.

Examples of agents include pyrolitic carbon, titanium-nitride-oxide,taxanes, fibrinogen, collagen, thrombin, phosphorylcholine, heparin,rapamycin, radioactive 188Re and 32P, silver nitrate, dactinomycin,sirolimus, everolimus, Abt-578, tacrolimus, camptothecin, etoposide,vincristine, mitomycin, fluorouracil, or cell adhesion peptides. Taxanesinclude, for example, paclitaxel, 10-deacetyltaxol,7-epi-10-deacetyltaxol, 7-xylosyl-10-deacetyltaxol, 7-epi-taxol,cephalomannine, baccatin III, baccatin V, 10-deacetylbaccatin III,7-epi-10-deacetylbaccatin III, docetaxel.

Of course, bioactive materials having other functions can also besuccessfully delivered in accordance with the variations describedherein. For example, an antiproliferative agent such as methotrexatewill inhibit over-proliferation of smooth muscle cells and thus inhibitrestenosis. The antiproliferative is desirably supplied for this purposeuntil the tissue has properly healed. Additionally, localized deliveryof an antiproliferative agent is also useful for the treatment of avariety of malignant conditions characterized by highly vascular growth.In such cases, an implant such as a implant could be placed in thesurgically created channel to provide a means of delivering a relativelyhigh dose of the antiproliferative agent directly to the target area. Avasodilator such as a calcium channel blocker or a nitrate may also bedelivered to the target site. The agent may further be a curative, apre-operative debulker reducing the size of the growth, or a palliativewhich eases the symptoms of the disease. For example, tamoxifen citrate,Taxol® or derivatives thereof Proscar®, Hytrin®, or Eulexin® may beapplied to the target site as described herein.

Variations of the invention may also include fibrinolytics such as tPA,streptokinase, or urokinase, etc. Such fibrinolytics prevent or reducethe accumulation of fibrin within the opening. Accumulation of fibrin inthe opening may result from inflammation of the tissue. The fibrin mayform a structure which makes it easier for tissue to grow into theopening using the fibrin structure as a framework. Use of fibrinolytics,either topically, locally, or on the implant, serves to remove or hinderthe network of fibrin from forming within the opening (or implant) andtherefore aids in modifying the healing response.

In the event that poisonous and toxic compounds are delivered, theyshould be controlled so that inadvertent death of tissue does not occur.The poisonous agent should be delivered locally or only be effectivelocally. One method for delivering the bioactive agent locally is toassociate the bioactive agent with an implant. For example, the implantsdescribed herein may include a bioactive substance or medicine depositedonto the interior, the exterior, or both the interior and exteriorsurfaces of the implant. The bioactive substance may remain on theimplant so that it does not leach. Cells that grow into the surgicallycreated channel contact the poison and die. Alternatively, the bioactiveagent may be configured to gradually elute as discussed below.

When used in the lungs, the implant modifies the healing response of thelung tissue (e.g., at the site of newly created hole/channel) for asufficient time until the healing response of the lung tissue subsidesor reduces such that the hole/channel becomes a persistent air path. Forexample, the implant and bioactive substance will modify the healingresponse for a sufficient time until the healing response is reducedand, from a visual observation, the body treats the opening essentiallyas a natural airway passage rather than as an injury to the airway wall.

In one variation of the invention which modifies the healing response asdescribe above, the implant provides a steady release rate of bio-activesubstance as well as has a sufficient amount of available bio-activesubstance to modify the healing response of the lung tissue. As notedherein, the term lung tissue is intended to include the tissue liningthe airway, the tissue beneath the lining, and the tissue within thelung but exterior to the airway (e.g., lung parenchyma.) Such a deliveryprofile allows for a concentration gradient of drug to build in thesetissues adjacent to the delivery site of the implant.

It is believed that forming the concentration gradient affects thehealing response of the lung tissue so that the implant does not becomeoccluded as a result of the healing response. Because the implant isoften placed in the airway wall it is exposed to the healing process ofthe multiple tissues. Providing a sufficient amount of bio-activesubstance allows for the formation of a concentration of the bio-activesubstance across these various tissues. In one variation of theinvention it is believed that the fluids from these tissues enter intothe composition layer of the device. The fluids then combine with thebio-active substances and migrate out of the composition layer to settleinto the lung tissue. A concentration gradient forms when the drug‘saturates’ local tissue and migrates beyond the saturated tissues.Furthermore, by providing a sufficient delivery rate, the healingresponse may be affected or suppressed during the critical timeimmediately after the wounding caused by creation of the collateralchannel when the healing response is greatest.

To select a proper combination of drug and polymer, it is believed thatthe solubility parameter of the polymer must be matched with thebio-active substance to provide an acceptable slow elution rate from thepolymer. Next, the polymer itself must be selected to have the properattributes, such as a proper diffusion coefficient (to slow fluidentering and departing from the implant), and proper mechanicalexpansion properties (to allow for the significant expansion of thepolymer to accommodate formation of the grommet shape.)

The solubility parameter is defined as the square root of the cohesiveenergy of the molecules in a compound. The level of control that apolymer has over the elution of a drug is the difference between thesolubility parameters of the polymer and the solubility parameter of thedrug. To select a polymer with the approximate diffusion a polymer witha high internal density could be selected to be less permeable to acomplex molecule such as paclitaxel. Using a polymer with high internaldensity also accommodated the significant expansion required of thepolymer to form the structure necessary to grommet about the airwaywall. An example of the polymer selection is found below.

It is also important to note that paclitaxel is a taxane that isregarded as a microtubule stabilizer. The benefits of a microtubulestabilizing substance for use in vascular drug eluting stents isdiscussed, for example, in U.S. Pat. No. 5,616,608 to Kinsella et al.This type of drug operates to enhance microtubule polymerization whichinhibits cell replication by stabilizing microtubules in spindles whichblock cell division. In contrast to the vascular applications, theimplant for use in one variation described herein may use microtubulestabilizing substances such as taxanes (e.g., paclitaxel) as well asthose microtubule destabilizing substances that are believed to promotemicrotubule disassembly in preventing cell replication. Suchdestabilizing substances include, but are not limited to vincristine,vinblastine, podophylotoxin, estramustine, noscapine, griseofulvin,dicoumarol, a vinca alkaloid, and a combination thereof.

Additionally, the exterior surface of the implant may be treated viaetching processes or with electrical charge to encourage binding of thebioactive substances to the implant. The exterior surface may also beroughened to enhance binding of the medicine to the surface as discussedin U.S. Pat. No. 6,918,927. See also U.S. Patent Publication No.2002/0071902, now abandoned, and U.S. Pat. Nos. 5,824,048 and 6,730,349which discuss various techniques for coating medical implants.

Although the implant may comprise a frame or body with a bioactivematrix disposed or otherwise associated therewith, the invention is notso limited. In one variation, the support member is formed from apolymer and the composition is joined to the polymeric support member.Alternatively, the bioactive substances may be placed directly onto thepolymeric support member.

Various additional substances may be used incorporated into the deviceto reduce an adverse reaction resulting from possible contact with theimplant and the airway wall. Adverse reactions include, but are notlimited to, granulation, swelling, and mucus overproduction. Thesesubstance may also be inhaled, injected, orally applied, topicallyapplied, or carried by the implant. These substances may includeanti-inflammatory, infection-fighting substances, steroids, mucalytics,enzymes, and wound healing-accelerating substances. Examples of thesesubstances include but are not limited to, acetylcysteine, albuterolsulfate, ipratropium bromide, dornase alfa, and corticosteroids.

As noted above, conventional vascular drug eluting devices are notdesigned for exposure multiple tissue environments. Moreover, thosedevices are placed in an environment where a constant flow of bloodcreates an environment requiring a different delivery mechanism andrate. As noted herein, experiments with conventional coronary drugeluting implants demonstrated that such devices were unsuitable.

Channel Creation Devices and Methods

As discussed above, the use of low temperature devices, (e.g.,mechanical devices, newer generation RF-type devices, etc.) to createthe channel may result in less trauma to surrounding tissue and minimizethe healing response of the tissue. FIGS. 4A-4C illustrates creation ofthe collateral channel and selecting a treatment site in the airway 100.As will be discussed in more detail below, a single device may be usedto select the site and create the channel. Moreover, another variationof the invention includes using such a device to deploy the conduit atthe target site. However, the one variation also contemplates usingseparate devices to perform each step or a combination of steps.

As shown in FIG. 4A, a device 602 is advanced, for example, via abronchoscope 404, into the airway 100. A potential treatment site isthen inspected to determine whether or not a blood vessel is inproximity to the site. Naturally, if a blood vessel is detected, thesurgeon has the option of selecting a different site. The device 602 maybe a Doppler ultrasound device, a thermal device, an imaging device,etc.

FIG. 4B illustrates another variation of selecting a site for a channel.In this variation, a piercing member (e.g., a blade affixed to a shaft,a needle, cannula, sharpened tube or rod, etc.,) 604 is advanced intothe airway wall. Once the piercing member 604 is inserted into theairway wall, the surgeon may inspect the area for blood to determinewhether the device punctured a blood vessel. After the opening iscreated the surgeon may also remove collect a biopsy of material behindthe airway wall. If the opening is large enough as created by a balloon,as described herein, the surgeon may use forceps to visually obtain thesample. This may be preferable to a blind method of obtaining biopsies,considering that the risk of bleeding may be reduced because the areahas been scanned for blood vessels.

The piercing member 604 may have a lumen and may be open at a distal endor closed. In those cases where the piercing member 604 is hollow andhas an opening at or near the distal end, the surgeon may aspirate thesite using the piercing member 604 to determine whether a blood vesselis present and/or penetrated. For example, flashback catheters containchambers which will fill with blood upon the penetration of a vessel bythe distal tip of the catheter. The piercing member may be incorporatedto have a flashback chamber to detect the presence of blood flow from apenetrated vessel. Using these approaches, a target site may not beselected until after a hole is made in the airway 100 wall. It should benoted that a piercing member may be of a diameter which results inclosure of the puncture site upon removal of the piercing member.Alternatively, the piercing member may be of a sufficient size orconstruction that the hole remains open upon removal of the piercingmember. In any case, the piercing member or another device may be usedto mark the site of the opening (e.g., via ink, dye, physical marker,via application of electrical energy, etc.) Furthermore, anothervariation includes use of both a detecting device as described above incombination with a piercing member. For example, the site may beinspected by the detecting device prior to insertion of a piercingmember.

The piercing member lumen may also used to deliver therapeutic fluids tothe lungs. For example, in case of bleeding after channel creation thephysician may apply epinephrine or saline the lungs. Alternatively thephysician may use the piercing member to apply epinephrine to the airwaywall prior to creation of the channel, to prevent bleeding. This may bedone by injecting directly into the airway wall at or about the site ofpassage creation; singly or in a surrounding pattern of multipleapplications. The physician may also use the piercing member lumen toapply any of the bioactive agents discussed herein, before or afterpassage creation.

Because it may be desirable to reach remote airways within the lung, itmay be necessary to fully articulate the scope 404 to access and inspecta desirable site. Therefore, to inspect the site and create an opening,it may be desirable to maintain the scope 404 in a fixed position andsimply advance/retract various components of the scope or devices in thescope. Accordingly, a piercing member may be selected to have a lengththat will sufficiently pass through the airway wall, while being smallenough that it will also pass through a fully articulated bronchoscope.Furthermore, the piercing member may have sections of varying stiffnesswhere a distal portion, (that is sufficient stiff to penetrate thetissue) may be of a length such that it is able to advance through afully articulated bronchoscope. For example, the piercing member maycomprised of a sharpened cannula which has a length from between 2 mm to30 mm. The diameter may range between 16 Ga to 25 Ga or larger. Thecannula may be affixed to a catheter having a relatively flexibleproximal portion. In any case, the length of the piecing member 604 mayvary as needed.

The piercing member is not limited to a cannula; it may be of solidconstruction, such as a sharpened rod or wire. Additionally the piercingmember may be adapted with an elongate member, such as a wire, rod, ortube, which extends throughout the device. The purpose of the elongatemember is to provide column strength to the piercing member andnecessary bending resistance to the catheter, because it has been foundthat the device must have high column strength to effectively pierce theairway wall, otherwise the device will deflect and not create apassageway. The elongate member may be utilized to expose and retractthe piercing member within the catheter, as the elongate member mayextend throughout the device to a user interface. The elongate memberand piercing member may also be constructed from one piece of material,thereby making them one part. Alternatively the elongate member may be aseparate part welded, bonded, mechanically attached, or a combinationthereof, to the piercing member.

However, it is understood, that the current invention is not limited toany particular length of the piercing member. Furthermore, the piercingmember may be comprised of a resilient polymer, a polymer with areinforced structure (e.g., a braid, coil, etc.), a super-elastic alloy,a metallic material with sufficient resilience, etc, such that it maynavigate through a fully articulated bronchoscope yet return to itsoriginal profile upon exiting the working channel of the scope.

In some variations of the invention, the piercing member of the devicemay be retractable within a lumen of an elongate shaft so as to preventdamage to the bronchoscope or to tissue as the device advances to thetarget site. Additionally the piercing member may be retracted after theinitial piercing of the airway wall, and blunt trauma may be used tofurther push the remaining portion of the catheter into the airway wall.This technique may help avoid additional bleeding and pneumothoraxesfrom an exposed piercing member. The catheter may be advanced totortuous locations; therefore the device may incorporate low frictionmaterials to make it easier to reach the treatment site. The materialsmay be selected from a group of low friction polymers, for example PTFE.Low friction materials may also be applied as a coating onto the piercedmember or elongate member, for example PTFE or titanium nitride.Reducing the contact surface area between the members may also help toreduce friction. Adding or removing material from the surfaces ofmembers is one way to reduce contact surface area. For example attachinga closed coiled spring around the piercing member or elongate member,effectively reduces the surface area contacted between the elongatemember and lumen because only the peaks of the coils contact the lumen.

In additional variations of the invention, as shown in FIG. 4C, aballoon catheter may be configured with a piercing member 604. In thisvariation the balloon 614 advances into the opening created by thepiercing member (in which case the piercing member either retracts intothe catheter or advances with the catheter.) The balloon 614 would thendeploy to dilate the opening for ease of later inserting a conduit.Alternatively, a conduit may be located on the balloon itself anddeployed on inflation of the balloon. Examples of variations of such aballoon catheter may be found below. Furthermore, the needle may beaffixed to a tapered introducer type device which is able to dilate theopening.

The piercing member 604 may also be used to deliver bioactive substances(as described herein) to the site of the opening. In such a case, thepiercing member 604 may deliver the bioactive substance during creationof the opening (e.g., see FIG. 4B) or after dilation of the opening (seee.g., FIG. 4C). In another variation of the invention, the piercingmember 604 may be have a multi-lumen cross-section with different lumensbeing reserved, for example, for inflating the balloon, aspirating thesite for blood, drug delivery, and suction of mucous/fluids at the site.In any of the variations described herein, an obturator (not shown) maybe used to fill a lumen during advancement of the piercing member intotissue so that the lumen does not become blocked with tissue or otherdebris. The obturator may be a guide-wire, polymeric column of material,etc.

FIG. 4D illustrates a variation of a balloon catheter 606 having apiercing member 604. In this variation, the balloon catheter 606comprises two lumens 608, 610. One lumen 608 is fluidly coupled to theinterior of the balloon 614 while the second lumen 610 extends throughthe piercing member 604. It is understood that the device 606 may beconfigured to have any number of lumens as required. As discussed above,the piercing member 604 may either be fixedly attached to the distal endof the balloon catheter 606. Alternatively, the piercing member 604 maybe retractable into the balloon catheter 606 so that it does not causedamage to lung parenchyma when the catheter 606 is inserted into theairway 100 wall. As illustrated, the balloon catheter 606 may have atapered section 612 between the piercing member 604 and the balloon 614to assist in insertion of the balloon 614 into the opening 112.

FIG. 4E illustrates an additional variation of a piercing member 604. Asillustrated, the piercing member 604 may have a number of ports 616(e.g., openings, holes, etc.). The ports 616 may allow for eitheraspiration of blood or delivery of bio-active substances as describedherein. Furthermore, although the piercing members 604 shown herein areconfigured with a beveled tip, it is contemplated that the tip may beany type of tip sufficient to penetrate the airway wall. For instance,the tip may be non-beveled with sharpened edges, the tip may be a trocartipped needle, or any other available needle tip configuration. Thepiercing member 604 of FIG. 4E is also shown with an obturator placedtherein. In this configuration, the obturator 618 blocks the lumen ofthe piercing member 604 at the distal end. Moreover, as shown, a portionof the obturator 618 may be sized such that it is smaller than a lumenof the piercing member 604 to allow for delivery of substances oraspiration through the ports 616.

FIG. 4F illustrates yet another variation of a balloon catheter 606having a piercing member 604. In this variation, as indicated by thearrow, the piercing member 604 is capable of being retracted into thecatheter 606. The ability to retract the piercing member 604 into thecatheter 606 reduces the possibility of the piercing member 604 causingdamage to any lung tissue that is behind the airway wall. Clearly, thisvariation combines the channel-making step with the conduit deploymentstep. Also, as shown in the figure, the catheter 606 may have a conduit202 placed over the balloon 614. Such a variation may create the openingor channel and then deploy the conduit 200 with a single device.

FIG. 4G illustrates another variation of a balloon catheter 606 wherethe piercing member 604 is slidably located within the catheter 606. Inthis variation, the catheter 606 contains an outer and inner sheaths620, 622 which define two lumens. The lumen defined by the inner sheath622 extends to the distal end of the catheter 606 and may be used todeliver bioactive substances, for suction, or for irrigation.

It is also contemplated that variations of the invention include apiercing member which is affixed to the catheter. Alternatively, thepiercing member could have a flexible body that extends through thecatheter to a proximal hub which is able to be coupled to a vacuumsource, a source of medication, etc. Furthermore, either the piercingmember and/or balloon catheter may be “pre-loaded” with a bioactivesubstance. Such a feature allows improves the precision of amount ofsubstance delivered to the desired site.

As mentioned above, the piercing member 604 may be of a sufficient sizeor construction that the hole remains open upon removal of the piercingmember. Once variation of this as shown in FIG. 4H, where the device hasa conical tip 658 with a lumen extending through out. A piercing member604 is extendable past the distal tip to pierce the airway wall, afterthe initial opening is made, the rest of the device can be driven intothe airway wall, gradually expanding the hole to a desirable diameterwhich allows the conduit to be subsequently placed.

The makeup of airway tissue may require a considerable amount of forceto create a channel with the piercing device. Therefore, it willgenerally be easier to create a channel if the device has sufficientcolumn strength to avoid bending of the device when applying a force atthe proximal end of the device.

Additional variations of the invention may incorporate a nondistensibleballoon to overcome the toughness of the airway tissue. Nondistensibleballoons are generally made up of relatively inelastic materialsconsisting of PET, nylons, polyurethanes, polyolefins, PVC, and othercrosslinked polymers. The makeup of airway tissue may be very tough andresist radial expansions. Therefore it will be generally easier toexpand the channel in the airway wall using high pressure nondistensibleballoons (>6 atm), which generally inflate in a uniform shape.

Nondistensible balloons will occupy a greater mass than distensibleballoons because they in an inelastic predetermined form. Too muchballoon mass will have too large of a working diameter, which in turnwill hinder entry into a channel. Working diameter is the smallesteffective diameter opening the uninflated nondistensible balloon can beinserted into. Therefore it is desirable to have the uninflatednondistensible balloon to have a working diameter close to the diameterof the piercing device 604. This can be attained by using a thin walledballoon, using a balloon with a small distal profile, by using a balloonwith a distal end which is close in actual diameter to the diameter ofthe piercing member, or by using a balloon which folds into a lowprofile state, or a combination of these.

As shown in FIG. 4I, a device of insufficient sharpness will “tent” theairway wall 450. Tenting occurs when a device is placed against anairway wall with significant force but with no puncturing of the airwaywall. The airway wall will deflect and become displaced until the deviceis withdrawn. If the tissue becomes tented there remains a significantamount of potential energy placed by the device onto the airway wall.The potential energy may unexpectedly becomes realized, when the deviceeventually punctures the airway, which may cause the device to suddenlyplunge into the parenchyma to an unintended depth. Plunging may in turncause unintended damage to the patient. A depth limiting feature 654 mayovercome this problem.

Variations of the invention include a depth limiting feature that mayprevent inadvertent advancement of the device when creating the channel.One example of this may be a circular tube 654 placed over the deviceand set at a fixed distance (e.g. 10 mm) from the distal tip of thepiercing member, proximal to the balloon, as shown in FIG. 4J. If thedevice does tent and plunge into the airway wall the front face of thetube may halt the plunging effect by acting as a barrier. Anotherexample would be a secondary balloon, proximal to the channel expansionballoon, placed in a similar position to the circular tube as describedabove. Another example would be a folding basket formed from the outerlumen of the device, or constructed from wire.

As shown in FIG. 4K, variations of the invention may include a distalcollar 650 on the distal portion of the piercing member 604 to preciselylimit the maximum extension and retraction of the piercing member 604.The distal collar 650 would be attached to the piercing member andtravel between two set collar stops 652 which are attached to the lumen656 the piercing member travels in. This feature has multiple benefits;first, it has the safety setting a maximum distance for the piercingmember to extend, around 2-3 mm has been found to be sufficient in mostcases. Thus, the maximum penetration of the piercing member 604 islimited which may prevent unintentional damage to the lung tissue.

The collar 650 protects the bronchoscope by preventing deflection of thedistal tip. Deflection can take place when there is a significant amountof gap between the inner sheath 622 and the distal tip of the piercingmember in the retracted mode. When the device is being maneuveredthrough a bronchoscope in a torturous configuration, the lumen 656 candeflect while the stiffer piercing member will not, and thus thepiercing member may pierce through the deflected lumen 656 andsubsequently into the bronchoscope. By setting a small gap (e.g. <1 mm)this deflection may be eliminated, and the scope protected.

The collar 650 also allows the piercing member to be reliably extended.It was found that when a similar feature was placed at the proximalsection of the device the piercing member could not reliably be extendedto a set distance beyond the distal tip. This is because when in atorturous configuration the outer sheath 620 of the device may have atendency to stretch or compress. As a result the tubing may stretch tosuch a degree that when the piercing member is fully extended it stillmay not fully extend past the distal tip of the lumen 656. By locatingthe collar 650 in the distal portion of the lumen 656 (e.g. less than 2inches from the distal tip) the stretching or compression is minimizedor eliminated.

Conduit Deployment Devices and Methods

FIGS. 5A-5C illustrate a way to deploy a conduit in a channel. Referringto FIG. 5A, a delivery device 400 is loaded with a conduit 200. Anaccess scope-type device 404 (e.g., an endoscope, a bronchoscope, orother device) may optionally be used to place the delivery device 400into a collateral channel 112. A guide wire 402 may be used to place thedelivery device 400 into the collateral channel 112. The guide wire 402may be a conventional guide-wire or it may simply be comprised of asuper-elastic material. The use of a guide wire is optional as thevariations described herein contemplate placement of the conduit 200using only the delivery device 400.

FIG. 5A also illustrates articulation (or bending) of the deliver device400 to access the collateral channel 112. However, the one variationalso contemplates articulation of the access device 404. The accessdevice 404 may be articulated such that the delivery device 400 mayadvance straight into the collateral channel 112. Accordingly, thedelivery device 400 may exit straight from the access device 404 or itmay be articulated into the opening.

FIG. 5B illustrates deployment of the conduit 200. In particular,balloon member 406 is shown in an expanded state resulting in (1) theconduit's center section being radially expanded and (2) the conduit'sextension members being outwardly deflected such that opposing extensionmembers sandwich portions of the tissue wall 422. Diametric-controlmembers 424 are also shown in this figure. The diametric orcenter-control segments limit the center section's radial expansion. Inthis manner, conduit 200 is securely placed in the channel to maintain apassageway through the airway wall 422.

FIG. 5C illustrates the deployed conduit 200 once the delivery device400 is removed from the site. It should be noted that dilation of thecollateral channel or opening 112 may be performed by mere insertion ofthe conduit 200 and/or delivery device 400.

It should be noted that deployment of conduits is not limited to thatshown in FIGS. 5A-5C, instead, other means may be used to deploy theconduit. For example, spring-loaded or shape memory features may beactuated by mechanical or thermal release and unlocking methods.Additionally, mechanical wedges, lever-type devices, scissors-jackdevices, open chest surgical placement and other techniques may be usedto deploy the conduit. Again, the conduit 200 may be comprised of anelastic or super-elastic material which is restrained in a reducedprofile for deployment and expands to its deployed state upon mechanicalactuator or release.

In one additional variation of the invention, as shown in FIGS. 5D, aconduit 201 may be deployed within a second structure such as a secondconduit or stent. Such an approach may be used to increase retention ofthe conduits within the channel as well as prevent closing of thechannel. For example, an initial conduit 200 or stent may be deployedwithin the channel 112. This first conduit or stent may have certainproperties that make it more acceptable to implantation within the bodywithout generating an aggressive tissue healing response. For instance,the stent may be a drug eluting stent, or the conduit may be constructedfrom a bio-compatible metal without any additional tissue barrier. Oncethe initial stent or conduit is placed within the channel 112 a secondconduit may be deployed within the first conduit. As shown in FIG. 5D, afirst conduit 200 (or stent) is placed within the channel 112. FIG. 5Dillustrates a second conduit 201 advanced towards the first conduit 200.FIG. 5E illustrates the second conduit 201 deployed within the firstconduit 200. The second conduit 201 may have additional properties thatpermit the channel to remain patent. For example, the second conduit 201my have a tissue barrier as discussed above, or other construction thatgenerates an aggressive healing response within the lung. Therefore, thefirst conduit 200, being more conducive to implantation, will serve toanchor both conduits 200, 201 as the tissue either does not grow, or itgrows around the outer conduit 200. The second conduit, for example, mayhave a tissue barrier placed thereon. Once the second conduit 201 isdeployed within the first conduit 200, the tissue barrier of the secondconduit 201 will prevent tissue from growing through the stentstructure. It should be noted that the structure of a conduit within aconduit may be incorporated into a single composite structure.

In use, the conduit 200 is deployed with the distal side towards theparenchymal tissue 460 while the proximal side remains adjacent or inthe airway 450. Of course, where the proximal and distal extensionmembers are identical, the conduit may be deployed with either sidetowards the parenchymal tissue.

FIGS. 6A-6B illustrate another example of deploying a conduit 500 in achannel 510 (or opening) created in a tissue wall 520. Referring to FIG.6A, a delivery tool 530 carrying a deployable conduit 500 is insertedinto the channel 510. The delivery tool 530 is extended straight from anaccess catheter 540 such that the delivery tool forms an angle

with the tissue wall 520. It is to be understood that while the tissuewall of airway 522 is shown as being thin and well defined, onevariation of a device described herein may be utilized to maintain thepatency of channels and openings which have less well definedboundaries. The delivery tool is further manipulated until the conduitis properly positioned which is determined by, for example, observingthe position of a visualization mark 552 on the conduit relative to theopening of the channel 510.

FIG. 6B illustrates enlarging and securing the conduit in the channelusing an expandable member or balloon 560. The balloon 560 may beradially expanded using fluid (gas or liquid) pressure to deploy theconduit 500. The balloon may have a cylindrical shape (or another shapesuch as an hourglass shape) when expanded to 1.) expand the centersection and 2.) deflect the proximal and distal sections of the conduitsuch that the conduit is secured to the tissue wall 520. During thisdeployment step, the tissue wall 520 may distort or bend to some degreebut when the delivery tool is removed, the elasticity of the tissuetends to return the tissue wall to its initial shape. Accordingly, theconduits disclosed herein may be deployed either perpendicular to (ornon-perpendicular to) the tissue wall.

FIG. 7A illustrates another variation of deploying a conduit 200 into anopening 112. In some variations of the invention, prior to deployment ofthe conduit 200, the channel 112 may have a diameter or size that mayrequire an additional dilation or expansion of the channel 112 forproper deployment of the conduit 200. For example, the channel 112 maybe created by a piercing member, as described above, where the channel112 nearly closes upon removal of the piercing member. However, thedevices and method described herein are not limited to channels 112 ofany particular size. The channels may in fact be larger than a diameterof the conduit 200 in its un-deployed state.

In any case, after creation of the channel 112 the surgeon may advance aballoon catheter 630 containing a conduit 200 towards the site of theopening 112. The variation of the balloon catheter 630 depicted in thefigure also includes a guide body 632. Because the opening 112 may bedifficult to locate, the guide body 632 may serve various functions toassist in locating the opening 112 and placing the conduit 200. Forexample, as shown in FIG. 7A, the guide body 632 may have a roundedfront surface. This allows probing of the catheter 630 against theairway 100 wall to more easily locate the opening 112. The roundedsurface of the guide body 632 will not drag on the airway tissue.

As shown in FIG. 7B, once inserted into the opening 112, the guide body632 provides an additional function of temporarily anchoring the device630 within the opening 112. The ability to temporarily anchor the device630 into the opening 112 may be desirable due to the natural tidalmotion of the lung during breathing. The increased surface area of theguide body 632 requires increased resistance upon remove the guide body632 from the opening 112. Such a feature lessens the occurrence ofunintended removal of the device from the site as the lung tissue moves.As shown in FIG. 7B, after insertion into the airway 100 wall, a portionof the guide body 632 serves as a resistance surface to provide thetemporary anchoring function. Additional variations of the guide body632 are shown below.

FIGS. 8A-8F illustrate additional variations of guide bodies 632 for usewith certain variation herein. As shown, the guide body 632 is locatedon the distal end of the balloon catheter 630. The guide body 632 willhave a front surface 634 that is preferably smooth such that it caneasily be moved over the airway wall. Proximal to the front surface 634,the guide body 632 will have at least one resistance surface 636 whichis defined as an area that causes increased resistance upon removal ofthe guide body 634 from the airway wall. As shown, the resistancesurface 636 will be adjacent to an area of reduced diameter 638 to whichallows the guide body 632 to nest within the opening 112 in the airwaywall. The guide body 632 may have any number of shapes as shown in thefigures.

FIG. 8F illustrates another variation of a guide body 632 having aresistance surface 636 which comprises an area of increased surfaceroughness such that the surface will drag upon the airway wall or tissuesurrounding the channel 112. Such a feature may be combined with thevariations of the guide members provided above.

The balloon catheters 630 in certain variations may include a dilatingmember between the guide body 632 and balloon 614. In the variationshown in FIG. 8A, the dilating member comprises a tapered section.However, the invention is not limited as such. For example, the dilatingmember may comprise a second inflatable balloon, or other expandingdevice. The dilating members may also be retractable within the elongateshaft.

FIGS. 9A and 9B depict cross sections of examples of a balloon catheter630 having a guide body 632 that includes a lumen 642 which terminatesat a surface of the guide body 632. The lumen 642 may be used forsuction, irrigation, or deliver bio-active substances, etc. The catheter630 may also have an additional lumens 646, 646, 648 as shown, forinflation of the balloon 614 and for additional suction 644, and forcommunication with the guide body lumen 642. As shown in FIG. 8B, thelumen may also be used to advance a piercing member 604 to the airwaywall to create the channel 112.

Any of the balloons described herein may be distensible balloons (e.g.,they assume a predetermined shape upon expansion) or elastic balloons(e.g., simply expand). Use of a distensible balloon permits control indilating the opening 112 or placement of the conduit.

Delivery of Medications/Substances to Parenchymal Tissue

In an additional variation, a medical practitioner may create a channelto delivery substances such as bioactive agents, medications,therapeutic substances, or other such materials through the airway walland directly to the parenchymal tissue of the lung.

In such a case, the practitioner engages many of the steps outlinedabove such as identifying regions of having severe occurrences oftrapped gas or tissue destruction. However, the methods and channelcreation techniques described herein may also be suitable for a varietyof other disease states affiliated with the lung (especially cancer andtreatment of tumors or other growths). In the latter cases, an x-ray,ultrasound, Doppler, acoustic, MRI, PET, computed tomography (CT) scansand/or other non-invasive imaging technique may be employed to locatethe region of diseased tissue (such as a tumor). In some cases, if thechannel is created solely for the purpose of delivering a substance,then the channel patency techniques described herein may no longer beapplicable. Instead, after delivery of the substance, the medicalpractitioner may desire closure of the channel.

Once the practitioner identifies a region for creation of the channel,the practitioner may then search for a safe location to penetrate theairway wall (such as using the blood vessel detection techniquesdescribed above.

Example Implant

Implants comprising stainless steel mesh frame fully encapsulated with acomposition comprising silicone (as described below) and paclitaxel wereimplanted in several canine models. Visual observation indicated that,on average, the passage through the implants remained unobstructed andwere associated with significantly reduced fibrotic and inflammatoryresponses, in canine models, at a considerably higher rate than animplant without any drug adjunct or coronary drug eluting stents (asshown in FIG. 12).

The composition comprised approximately a 9% paclitaxel to siliconeratio with approximately 400 micrograms of paclitaxel per implant.Measurements found that approximately 30% of the paclitaxel releasedafter 60 days. In general, for implants with the paclitaxel/siliconecomposition, observations of chronic inflammation, epithelial metaplasiaand fibrosis were all very mild.

For paclitaxel as the bioactive substance, polymers with solubilityparameters between 5-25 (MPa) ̂½ were believed to provide sufficientelution rates. The polymer used in the example device has gooddiffusivity for lipophilic drug (such as paclitaxel) because the sidemethyl group on the silicone may be substituted with more lipophilichydrocarbon molecules containing vinyl group or groups in additionpolymerization by platinum catalyst.

The composition for the example may be as follow: polymer part:polydimethylsiloxane, vinyldimethyl terminated, any viscosity; and/orpolydimethylsiloxane, vinylmonomethyl terminated, any viscosity. Thecross-linker part: polydimethylsiloxane, any viscosity; and orpolymonomethylsiloxane, any viscosity. Platinum catalyst part and/orcross-linker part: platinum; and/orplatinum-divinyltetramethyldisiloxane complex in xylene, 2-3% Pt; and/orplatinum-divinyltetramethyldisiloxane complex in vinyl terminatedpolydimethylsiloxane, 2-3% Pt; and/orplatinum-divinyltetramethyldisiloxane complex in vinyl terminatedpolydimethylsiloxane, ˜1% Pt; platinum-Cyclovinylmethylsiloxane complex,2-3% Pt in cyclic vinyl methyl siloxane.

These components may be combined in different ratios to make thepolymer. The hydrocarbon side chain off the silicone back bone makesthis polymer system unique and may result in a “zero-order”-like releaseprofile. The amount of vinyl siloxane cross-linker may determine therate of the drug release and diffusivity of the polymer to the drug.There are other types of polydimethylsiloxanes such as: trimethylsiloxyterminated polydimethylsiloxane in various viscosities, (48-96%)dimethyl (4-52%) diphenylsiloxane copolymer in various viscosities,dimethylsiloxane-ethylene oxide copolymer, dimethyl diphenylsiloxanecopolymer, polymethylhydrosiloxane, trimethylsilyl terminated at variousviscosities, (30-55%) methyldro-(45-70%) dimethylsiloxane copolymer atvarious viscosities, polymethylphenylsiloxane, polydimethylsiloxanesilanol terminated at various viscosities, polydimethylsiloxaneaminopropyldimethyl terminated at various viscosities. For paclitaxel arelease profile was found to be acceptable with a polymer systemconsisting of polydimethylsiloxane vinyl terminated at various viscosityand a range of platinum-mono, di, tri and/or tetramethyldisiloxanecomplex.

After finding a suitable location, the practitioner creates the openingor channel. Again, any technique described herein may be used to createthe channel. However, FIG. 10A illustrates an example in which asubstance may be delivered during creation of the channel. In thisexample, a similar balloon catheter 606 as described above may have apiercing member 604 that penetrates the airway wall 450. Once through,the practitioner may inject the desired substance into parenchymaltissue 460. Although the illustration shows the piercing member 604 asextending slightly past the airway wall 450, variations of the methodinclude delivering a substance to any location beyond the wall.

FIG. 10B illustrates another variation of the method. As shown, asubstance may be delivered through an existing channel/opening 112.While method may include delivering the substance through a opening 112with or without an implant 200. In this variation, the channel 112 alsoincludes an implant 200 within the opening 112 with the substance beingdelivered through the implant 200. Use of an implant 200 may bedesirable in those cases where trapped gasses must be evacuate as wellas those cases where repeat treatment of a site is planned (e.g., tumortreatment). In addition, the implant 200 may be removed from the channel112 to either promote or inhibit healing depending on the desiredbenefit. Naturally, this treatment may be performed in more than onelocation in the lung, depending on the areas of intended treatmentand/or diseased tissue.

The substances that may be delivered as described above may include anyof the substances described herein. In addition, examples of bioactivesubstances include, but are not limited to, antimetabolites,antithrobotics, anticoagulants, antiplatelet agents, thorombolytics,antiproliferatives, antinflammatories, agents that inhibit hyperplasiaand in particular restenosis, smooth muscle cell inhibitors, growthfactors, growth factor inhibitors, cell adhesion inhibitors, celladhesion promoters and drugs that may enhance the formation of healthyneointimal tissue, including endothelial cell regeneration. The positiveaction may come from inhibiting particular cells (e.g., smooth musclecells) or tissue formation (e.g., fibromuscular tissue) whileencouraging different cell migration (e.g., endothelium, epithelium) andtissue formation (neointimal tissue).

Still other bioactive agents include but are not limited to analgesics,anticonvulsives, anti-infectives (e.g., antibiotics, antimicrobials),antineoplastics, H2 antagonists (Histamine 2 antagonists), steroids,non-steroidal anti-inflammatories, hormones, immunomodulators, mast cellstabilizers, nucleoside analogues, respiratory agents,antihypertensives, antihistamines, ACE inhibitors, cell growth factors,nerve growth factors, anti-angiogenic agents or angiogenesis inhibitors(e.g., endostatins or angiostatins), tissue irritants (e.g., a compoundcomprising talc), poisons (e.g., arsenic), cytotoxic agents (e.g., acompound that can cause cell death), various metals (silver, aluminum,zinc, platinum, arsenic, etc.), epithelial growth factors or acombination of any of the agents disclosed herein.

Examples of agents include pyrolitic carbon, titanium-nitride-oxide,taxanes, fibrinogen, collagen, thrombin, phosphorylcholine, heparin,rapamycin, radioactive 188Re and 32P, silver nitrate, dactinomycin,sirolimus, everolimus, Abt-578, tacrolimus, camptothecin, etoposide,vincristine, mitomycin, fluorouracil, or cell adhesion peptides. Taxanesinclude, for example, paclitaxel, 10-deacetyltaxol,7-epi-10-deacetyltaxol, 7-xylosyl-10-deacetyltaxol, 7-epi-taxol,cephalomannine, baccatin III, baccatin V, 10-deacetylbaccatin III,7-epi-10-deacetylbaccatin III, docetaxel.

In addition, the substances may be selected to induce a biologic lungvolume reduction such as by using a talc compound, lung irritant, orfibrin hyrogels containing fibroblast growth factor −1. The use of suchcompounds may be found in: U.S. patent application Ser. No. 09/590,790,filed Jun. 8, 2000, now abandoned, entitled MINIMALLY INVASIVE LUNGVOLUME REDUCTION ASSEMBLY AND METHOD; U.S. patent application Ser. No.10/679,065 filed Oct. 3, 2003, now abandoned, entitled MINIMALLYINVASIVE LUNG VOLUME REDUCTION ASSEMBLY AND METHOD; and FIBROBLASTSGROWTH FACTOR-1 THERAPY FOR ADVANCED EMPHYSEMA—A NEW TISSUE ENGINEERINGAPPROACH FOR ACHIEVING LUNG VOLUME REDUCTION to Ingenito et al. J.Bronchol, Vol. 1, 3 Jul. 2006.

Various procedures described herein and below may be performed throughan extra-anatomic opening, opening, port or channel through an airwaywall in the lung or respiratory system. Various devices or instrumentsmay be advanced within or to the airway and out through anextra-anatomic opening or port or surgically created opening, port orchannel through an airway wall, into the lung tissue, parenchyma orother tissue in the body, where the devices or instruments may be usedto perform a variety of procedures on various tissues within the body.Various methods, devices and systems for diagnosing, monitoring, and/ortreating medical conditions through an extra-anatomic opening or portthrough or in an airway wall are described in detail below. In certainvariations, the opening, port or channel may be held open by placing atemporary or permanent structure such as a stent, shunt, or sheath inthe opening, through which to operate and/or advance other devices,instruments, compositions and/or drugs. One or more, e.g., multiple,openings, ports and/or channels may be created (with or without multipletemporary or permanent structures) to provide different access points tothe target regions, e.g., to access a tumor, nodule, lymph node or othertissue for assessment, monitoring, destruction, or removal.

A variety of procedures may be performed through an extra-anatomicopening or port through an airway wall including for example: diagnosticsampling; visual imaging; instilling or delivering drugs; microscopicimaging such as optical coherence tomography (OCT); tissue ablation,e.g., cryo, ultrasound, microwave, laser, radiofrequency (RF), etc.;injection of various substances, e.g., stem cells, antibiotics,antiproliferitives, chemo therapy agents; use of an excision or cuttingsnare; removal; resection; use of forceps; placing markers or fiducials;tissue or organ modification, implantation of various artificialstructures, and hypothermia procedures.

FIG. 11 illustrates one variation of a device for creating a supportstructure for an airway, such as a floppy airway, which expands and/orholds or stents open the lumen of an airway. Various conditions, e.g.,emphysema, cause lung tissue and parenchyma destruction, which resultsin airways becoming floppy and losing their rigidity. When air is drawnthrough an airway having these conditions, the airway tends to collapsedue to the Bernoulli effect, trapping gas and causing the lungs tobecome hyperinflated.

As shown in FIG. 11, a clamp 700 may have a grasping end 701 and ananchoring end 702. In use, the clamp may be advanced through theextra-anatomic opening or port in the airway wall, into the parenchymawhere the grasping end is used to capture or grab healthier parenchyma,which is not immediately adjacent to the airway wall, but sits beyondthe destructed tissue. The anchoring end 702 of the clamp remains withinthe airway lumen, allowing the clamp 700 to tether the capturedparenchyma to the airway wall. As a result of the tethering, thecaptured parenchyma will exert a pulling force on the anchored clamp,pulling on the airway wall such that the airway lumen remains open anddoes not collapse on itself. The tethering may prevent the airway lumenfrom collapsing or substantially narrowing in diameter.

Any device or mechanism that may be used to capture and tetherparenchyma to an airway wall may be utilized. Examples include but arenot limited to, clamp made from various materials, e.g., nitinol, or asuture for anchoring parenchyma to an airway wall. The anchoring end 702may include a t-bar or other design for anchoring the clamp 700 to theairway wall, preventing the clamp 700 from being pulled completelythrough the extra-anatomic opening or port and out of the airway. Anydevice that applies enough force to break the Bernoulli effect on theairway walls and prevent collapsing of the airway lumen on itself may beutilized. In certain variations, the grasping end of the clamp may be at-bar, a barb, or a hook.

FIG. 12 illustrates another variation of a device for creating a supportstructure for an airway or floppy airway, which expands and/or holds orstents open the lumen of an airway. An anchor 740 is provided, the firstend of the anchor includes a t-bar and the second end includes a t-bar.The anchor may also be in the form of a hook, barb, suture, loop, orplate. The anchor 740 may be advanced through an extra-anatomic openingor port of a first airway and into a second airway, advancing throughdestroyed lung tissue or parenchyma in between, and anchoring the firstand second airways to each other. The t-bars at either end of the anchorwill be forced against the inner airway wall of the respective airwaysin which they are positioned, pulling the airways toward each other. Asa result, the airway walls may be pulled away from the center of therespective airway lumen, and the airway lumen of each airway may be heldopen, preventing the airway walls from collapsing on themselves andpreventing the airway lumen from collapsing or substantially narrowingin diameter.

FIG. 13 illustrates one variation of a device for creating a channel orpathway through an extra-anatomic opening or port in an airway wall,through which instruments or tools may be passed. The device 710 mayinclude an outer tube 711 and an inner tube (not shown). In use, theouter tube 711 is passed through an extra-anatomic opening or port inthe airway wall. The inner tube is advanced through the outer tube 711.The device 710 is clamped to the airway wall, providing a passagethrough which various instruments or tools may be passed. The passagemay extend any distance beyond the extra-anatomic opening or port intothe lung tissue and may also extend from the airway wall back into theairways some distance including up to the mouth or nose, or it may bepositioned inside a scope. The device 710 may provide an artificialchannel for the advancement of an instrument, e.g., for procedures whereseveral passes of an instrument are required to effect treatment. In onevariation, an instrument may make several passes through the artificialchannel created by device 710 in order to break up and/or remove a largemass of tissue. In another variation, it may be used to reliably returnto a site so that multiple tissue samples can be taken. In yet anothervariation, it may be used to deliver multiple doses of a substance orsubstances to the lung tissue. In all of these cases, it may be left inplace temporarily, e.g. during a single procedural, or for longerperiods of time, e.g. over multiple procedures across several or manydays.

FIG. 14 illustrates another variation of a device for deliveringinstruments or tools through an extra-anatomic opening or port in anairway wall. A device in the form of a catheter 750 or other elongateinstrument, such as a steerable or non-steerable catheter, deliverycatheter, or guide sheath may be provided and advanced through anextra-anatomic opening or port in an airway wall. The catheter mayinclude a needle 752 or sharpened tip at its distal end, allowing thecatheter to be advanced or driven through tissue to reach a targetdestination. It may also include a rounded tip to dissect through lessdense tissue. The catheter may include an electromagnetic or magneticchip 751, sensor or other tracking device at its distal end tofacilitate navigation and/or tracking of the catheter to position thecatheter at the target destination. For example, an externalelectromagnetic field or electromagnetic sensor may be utilized to guideand/or track the catheter or any other devices or substances deliveredfrom the elongate instrument or catheter. The electromagnetic field maybe movable.

In certain variations, navigation technology that incorporates otherforms of real time imaging such as ultrasound, fluoroscopy, CT, MRI, orPET may be utilized to guide or track the catheter as it is moved oradvanced through tissue. Once the catheter is positioned at the targetdestination, the catheter may act as a platform through which variousinstruments and/or tools may be delivered. For example, biopsy forceps,forceps, injection needles, ablation and/or cryoablation catheters maybe delivered through the catheter and through the extra-anatomic openingor port in the airway wall, to a target site to perform the desiredprocedure.

In certain variations, the electromagnetic field may be registered to a3D model of the lung which has been reconstructed from a set ofradiographic images. The radiographic images may be from a CT scan.

In one example, a target tumor may be identified and/or tracked usingthe aforementioned navigation technology. The catheter may be navigatedthrough an extra-anatomic opening or port in an airway wall, toward thetarget tumor, using an electromagnetic field. An instrument may then beadvanced through the catheter, guide sheath or delivery catheter, to thetumor to perform the desired procedure.

Various devices or methods for collapsing lung tissue or parenchymaand/or providing a compression system for a damaged or injured lungtissue where the lung tissue or parenchyma is accessed through anextra-anatomic opening or port in an airway wall are provided. A clampmade from a shape memory metal and having a variety of shapes may beutilized. In use, the clamp may be advanced through an extra-anatomicopening or port in an airway wall and into parenchyma or lung tissue.The clamp may expand upon exiting the extra-anatomic opening or port andit may grab, push, pull, compress, extend, collapse, or reshapeparenchyma or lung tissue.

In one variation, as illustrated in FIG. 15, the clamp may be in theform of a butterfly clamp 720. The butterfly clamp 720 may be made froma shape memory material. The butterfly clamp 720 is advanceable throughthe airway and through the extra-anatomic opening or port in the airwaywall in a straight wire configuration. In order to maintain the clamp ina straight wire configuration, it may be deployed from a semi rigidtubular member which has been fed into the airways from the mouth ornose with or without the use of a bronchoscope. Upon exiting the airwayvia the extra-anatomic opening or port, the butterfly clamp 720 becomesunconstrained and reverts to a predetermined expanded shape. The end ofthe clamp that remains inside the airway lumen may include one or moreanchors or barbs which may penetrate into the airway wall.

In use, the butterfly clamp 720 is advanced through the extra-anatomicopening or port in the airway wall and into the lung tissue orparenchyma. The butterfly clamp expands into a predetermined shape uponexiting the extra-anatomic opening or port. The butterfly clamp graspsor attaches to destructed lung tissue or parenchyma. The clamp may bescrewed, twisted or cranked down, bringing the opposing ends of theclamp toward each other and toward the airway wall. As the butterflyclamp is cranked down, it compresses and/or collapses the graspeddestructed lung tissue or parenchyma, and the anchors are forced intothe inner airway wall. The anchors insert themselves into the airwaywall, anchoring down the clamp and preventing the clamp from untwistingor unwinding.

In any of the variations described herein, the device may be advancedthrough an extra-anatomic opening or port in an airway wall, into lungtissue or parenchyma and return into the airway via a second site orsecond extra-anatomic opening or port located at a different position onthe airway wall. Accordingly, a first end and second end of a devicecould both be positioned within the airway. In certain variations, oneor both ends may include an effector element, e.g., an electrode forproviding stimulation to tissue, and a center portion of the device,which remains outside of the airway and within the lung tissue orparenchyma, may include an effector element for treating, collapsing,and/or compressing destructed lung tissue or parenchyma. In onevariation, a device may be in the form of a vent tube which extendsoutside of the airway at a first location, through lung tissue orparenchyma, and back into the airway at a second location. The vent tubemay act as a French drain. Optionally, a device may return to the airwaylumen through the same extra-anatomic opening or port through which thedevice exited.

In another variation, a method for reducing the volume of bullae orother tissues or portions in the lung, via an extra-anatomic opening orport in an airway wall is provided. A needle may be advanced through anextra-anatomic opening or port in an airway wall to a bulla where theneedle is used to suck fluid or air from the bulla. A sclerosing agent,e.g., talc, hypertonic saline, sodium neododeclyl chloride, ortetracycline aqueous solution, may be inserted into the bulla to coatthe inside surface of the bulla to keep the bulla collapsed, flat, orclosed. The suction step and the step of injecting a sclerosing agentmay take place in any order or simultaneously. In certain variations, asealant or sealer may be injected into a bulla prior to sucking air outof the bulla, to seal any holes or leaks that may exist in the bulla. Abulla may be located or targeted using a CT scan or other visualizationtechnique.

Another variation of a method for reducing the volume of bullae via anextra-anatomic opening or port in an airway wall includes injecting orinserting a sclerosing agent, e.g., talc, hypertonic saline, sodiumneododeclyl chloride, or tetracycline aqueous solution, and optionally avisualizing agent, e.g., contrast agent into a bulla. The sclerosingagent and visualizing agent may be mixed to form a slurry or solutionand the solution may be injected into a bulla. The solution may seal offany collateral ventilation or openings in the bulla, while optionallyallowing for visualization of the bulla. The bulla may then be suctionedand/or flattened down, leaving all or some of the sclerosing agent toremain in the bulla, which sclerose or adhere the inner surfaces ofbulla to each other to keep it flattened and compressed down.

In certain variations, a sclerosing agent/contrast solution may beinjected into a bulla and visualized, e.g., under fluoroscopy. Byobserving or visualizing where the solution migrates in the lung, it maybe determined whether the bulla is closed off to collateral air channelsor not. If visualization shows that the solution remains in a closed offor confined area, suction may be applied to the bulla to suck down orflatten the bulla. In certain variations, a rigid bronchoscope, customrigid scope, or flexible bronchoscope or other scope may be utilized toreach an extra-anatomic opening or port in an airway or to reach theupper lobes of a lung for delivery of the solution and suction device. Alarge lumen needle may be utilized to suction and remove air or otherfluid from the bulla.

In another variation, as shown in FIG. 16, the inside surface of a bullamay be coated with an adhesive or wound closing or sealing material. Thebulla may be collapsed with vacuum and the adhesive or wound closing orsealing material may maintain the bulla in a collapsed state orpermanently collapse the bulla. The adhesive or wound closing or sealingmaterial may be delivered into the bulla from the distal end of acatheter via an extra-anatomic opening or port in an airway wall. Aproximal end of the catheter may have an interface to deliver and/orremove adhesive or wound closing or sealing material. In one variation,a multi-lumen catheter may include a lumen for delivery or removal of anadhesive, wound closing or sealing material, or other material; theother lumen may comprise a vacuum lumen. Also, a balloon or expandablemember on the outer surface of the catheter may be expanded to sealproximal to a treatment site. In one variation, a bulla may be accessedvia an extra-anatomic opening or port in an airway wall. Adhesive may bedelivered into a bulla and then excess adhesive may be removed andvacuum is applied to collapse the bulla. The vacuum may continue to beapplied until the adhesive sets.

In another variation, methods and devices are provided for treatingemphysema or other conditions by trapping or compressing destructed lungtissue in hyperinflated areas of the lung and reducing the amount oftrapped air in the hyperinflated areas of the lung. A barbed wire, e.g.,a nitinol wire, may be inserted through an extra-anatomic opening orport in an airway wall and into a hyperinflated area of the lung. Thelung tissue attaches or sticks to the barbed wire. The tissue is closeddown around the wire and the tissue necroses to the wire over time. Thisresults in less tissue and air filling up a patient's lung, which allowsthe diaphragm to raise up, so the patient can breathe more efficiently.In an alternative variation, an adhesive or sticky substance or flypaper may be used to grab and close down or reduce the size of thehyperinflated tissue. The respiratory function of the lung may create asuction that continuously pulls down areas of tissue, causing the tissueto glob together on the barbed wire or adhesive, thereby reducing thesize of the large hyperinflated area.

In another variation, a lapband or other cinching device may beintroduced through an extra-anatomic opening or port in an airway wallto compress hyperinflated segments of a lung. The lapband or cinchingdevice may be placed around a lobe or section of a lobe of the lung andcinched down to condense or reduce the amount of hyperinflated tissue inthe lung.

Another method for compressing hyperinflated segments of a lung includesfilling at least part of the pleural space with an expandable material.The expandable material provides as an external compression force. Forexample, where an upper anterior segment of the left lung ishyperinflated, the lung may be accessed via an extra-anatomic opening orport through an airway wall (or alternatively from outside the lung) andan extrapulmonary blob of silicone or other material may be injectedinto the pleural space. This results in compression of that segment ofthe lung and prevents the lung segment from reexpanding orhyperinflating.

FIG. 17 illustrates another device and method for compressinghyperinflated segments of a lung, which includes inserting a collapsibleballoon 721 (elastic or inelastic) through an extra-anatomic opening orport through an airway wall and into the lung. The outside of theballoon may be covered with barbs 722 or an adhesive for grabbingtissue. The balloon 721 is expanded in the lung bulla or segment, andthe outer surface of the balloon 721 sticks to and grabs the innersurface of the wall of the lung bulla or segment. The balloon 721 isallowed to collapse, deflated or suctioned down—the entry port of theballoon may optionally be sealed to prevent re-expansion—causing thelung bulla or lung segment or tissue to collapse and compress down withthe balloon. The balloon 721 coats the inner wall of a bulla or lungsegment and prevents collateral ventilation from refilling the collapsedportion of the lung.

The balloon 721 may break up lung tissue or parenchyma as it isexpanded. In one example, a glutaraldehyde based adhesive may be appliedto the outer surface of the balloon. Optionally, a grommet 723 or plugmay be used to plug the airway opening or port to the collapsed bulla orsegment of the lung to keep the segment collapsed and sealed. The plugmay be inserted through the opening in the airway wall. A variety ofballoons or other structures may be used to collapse the lung segment.For example, the balloon may be porous, able to secrete an adhesive orother substance. The balloon may be made of collagen, e.g., where theballoon is nonelastic and folded down on itself. Optionally a cage whichis mechanically expandable and collapsible may be used instead of aballoon. A balloon may be allowed to collapse or the air may be suckedfrom the balloon.

Another method for compressing hyperinflated areas of a lung includesinserting one or more anchors with lines connecting the anchors throughan extra-anatomic opening or port in an airway wall, into a bulla orlung segment. The anchors insert into the bulla or lung segment wall ortissue and the lines are pulled down to collapse and hold down the bullaor lung segment. Alternatively, a lobe or section of a lobe may becollapsed or folded over on itself and closed off by inserting abendable wire or rod through an opening or port in an airway wall and/orthrough the pleura. The wire or rod may be bended to mechanically folddown and retain the lobe in a collapsed state, preventing it fromrefilling with air. Alternatively, a lobe may be removed through anextra-anatomic opening or port in an airway, e.g., after the lobe hasbeen excised, cut up, or broken down by morcellation.

Methods for performing minimally invasive lung volume reduction surgeryvia an extra-anatomic opening or port in an airway wall, to removetrapped gas and prevent gas from refilling the lung or re-accumulatingin the lung, is provided.

In another variation for reducing the volume of a tissue mass or tissuevoid or bulla in a lung via an extra-anatomic opening or port in anairway wall thermal energy may be applied to shrink tissue, where thethermal energy may be delivered via an extra-anatomic opening or port inan airway wall. Thermal energy may be applied to various lung tissues,including, airway walls, blood vessels, parenchyma tissue, othercollagen tissue and other components of the lung in a manner sufficientto cause the tissue to shrink. For example, the thermal energy may bedelivered at 75° Celsius. for about 20 seconds or greater to effecttissue shrinkage. After the tissue is reduced in size, the smaller “atrest” size of the tissue may act as though its spring constant has beenincreased, restoring driving force and/or force balance of the tissue.Various forms of thermal energy at various frequencies may be utilized,including, for example, light energy, laser light energy, microwaveenergy, radio frequency, direct electrical resistivity of tissue (e.g.,DC, AC, or RF), conductive heat transfer from a heated probe orinstrument, hot fluid or gas, frictional thermal energy (e.g.,ultrasonic, RF, or slower oscillating motion probe), and/or chemicalreactions which release heat. The application of thermal energy may belocalized and used for treating specific segments of the lung or airwayor the energy may be applied grossly to treat an entire lung or lobe,e.g., with microwave.

In another variation for reducing the volume of a tissue mass in a lunga mechanically elastic or elastic member may be applied to a lung, viaan extra-anatomic opening or port in an airway wall. An elastic membermay be affixed to tissue within a lung. For example, an elastic band orspring may be anchored at two points within a lung to compress thetissue therebetween. An elastic member or spring may have each endaffixed or anchored to a different branch of an airway or to separatelocations on or within an airway (See FIGS. 18A-18B).

The methods and devices described above and herein may be used fortreating emphysema and/or other conditions.

In another variation, a method for performing a minimally invasiveprocedure through one or more extra-anatomic openings or ports in anairway wall is provided. For example, as illustrated in FIG. 19,multiple extra-anatomic openings or ports may be provided at differentlocations in airway walls where one or more devices may be advancedthrough each of the extra-anatomic openings or ports. The devices may betriangulated through the various openings or ports to a target locationor position to perform a desired procedure on a target tissue. Thedevices may be triangulated, positioned or located using a variety ofimaging technologies or methods, including, e.g., video assistance,similar to the technique used for VAT procedures.

FIG. 20 illustrates a variation of a device and method for performingimaging which can be used to determine the position of devices whenperforming procedures through a port in an airway wall. A coherent lightsource 761, e.g., a diode laser, may be placed on the tip of a firstcatheter 760 (e.g., a tx catheter) or treatment catheter, which catheteris advanced through an extra-anatomic opening or port in an airway wall.One or more sensors 762, e.g., two sensors, may be positioned on asecond catheter 763, which catheter is positioned within an airway.

In use, differential light power may be utilized to triangulate in onthe location of the tip of the first catheter 760. The sensors 762 mayeach sense a brightness of the light emitted from the light source 761on the first catheter 760, through tissue, and the sensed brightness maybe utilized to calculate the distance and direction of the firstcatheter 760, through tissue. Bright light can go through the airwaywall, and tissue in general, allowing the sensors 762 to sense or detectthe emitted light. Where the emitted light is coherent, wavelengths ofthe light may be measured to determine the distance of the catheter 760and may provide an exact measurement of the distance of the firstcatheter 760 relative to the sensors 762. In certain variations,differential sensing with a or of a pulsing coherent light source mayprovide an exact distance measurement from the sensors, e.g., a distancemeasurement of the first catheter 760 relative to the sensors 762.

FIG. 21 illustrates a variation of a device and method for performing anultrasound or other imaging through an extra-anatomic opening or port inan airway wall. A guided probe 770 having a front facing ultrasoundtransducer 771 may be advanced within an airway via a scope 772. Theprobe and/or ultrasound may be advanced through an extra-anatomicopening or port in an airway wall, and out of the airway into the lungtissue or parenchyma. The ultrasound may be used, e.g., to guide abiopsy procedure, or to visualize or guide other procedures,extraluminally or outside of the airway. The ultrasound may be utilizedto take an image or shot of the tissue or parenchyma outside and/orbehind the airway wall and/or to identify any areas for treatment. Inanother variation, one or more parameter of the ultrasound may be variedto improve the image or to deliver therapeutic doses of ultrasound tothe tissue to change the properties of the tissue. In certainvariations, an ultrasound guided extraluminal device may be provided.

In certain variations, a working channel may be established through anextra-anatomic opening or port in an airway wall and/or through lungtissue or parenchyma outside of the airway for performing procedures orextraluminal procedures. For example, after advancing ultrasound throughan extra-anatomic opening or port in an airway wall and visualizing andidentifying an area of interest in the lung tissue or parenchyma, aworking channel may be established through the lung tissue orparenchyma, such that other instruments or tools may be advanced orreturned to the area of interest for performing various extraluminalprocedures, e.g., biopsy.

In another variation, a device and method for removing a nodule fromlung tissue or parenchyma via an extra-anatomic opening or port in anairway wall is provided. The device may include an elongated member,e.g., a catheter or coil, having a cutter, e.g., a rotational cutter, atits distal end. In use, the catheter may be advanced through anextra-anatomic opening or port in an airway wall to a target nodule,tumor or other tissue. The cutter may morcellate, chew, or breakup thenodule or tumor. Chunks of the tumor are then pulled through thecatheter and removed through the extra-anatomic opening or port in theairway wall. The nodule or other tissue may be removed via a catheterand/or bronchoscope.

FIG. 22 illustrates one example of a cutting catheter which may beadvanced through an extra-anatomic opening or port through an airwaywall for the removal of nodules, cancerous tissue or other tissue.Flexible catheter 800 includes a cutting tip 801 and may have a catheterhousing (not shown), providing a tube within a tube configuration. Thecutting tip may include a cutting window 802. For example, a sharpenedcutting window 802 may be opened upon rotation of the cutting catheterwithin a housing, which causes tissue in the window to be cut. Cuttissue may then be suctioned through the catheter lumen. Fluid may beused to assist in the removal of cut tissue. The catheter may beflexible with rotational stiffness. A rotating member may rotate thecatheter 800 within the catheter housing. The catheter may providecutting action in multiple directions. For example, a catheter mayprovide rotational cutting action and/or front facing cutting action(e.g., where the catheter has an auger tip. Tissue may be capturedbetween an exposed auger and a cutting edge. A catheter may be made ofnitinol and/or include coil springs. In certain variations, rotation ofthe catheter may transport removed material axially down and through acatheter lumen for removal from a patient's body.

FIG. 23 illustrates a variation of a device and method, including acatheter 780 and a sponge 781 attached to the catheter 780. A sealantmaterial, e.g., a glutaraldehyde based cement may be placed on thesponge 781. In use, the catheter 780 with sponge 781 having a sealantmaterial may be advanced through an extra-anatomic opening or port in anairway wall and into a track made previously in the lung tissue orparenchyma by a catheter or other instrument to take a biopsy, or bxsample or to remove tissue. Delivery of the sealant material along thetrack seals the track in order to prevent the occurrence of apneumothorax or air leak in the lung. Alternatively, the sealantmaterial may be delivered from the tip of a catheter inserted throughthe extra-anatomic opening or port. The tip of the catheter may includesmall holes to allow the sealant to be dispersed evenly. The holes mayalso be disposed about the circumference of the distal end of thecatheter.

FIG. 24 shows a variation of a biopsy sampler. The biopsy sampler has acatheter 790. Actuateable anchors 791 or barbs are positioned at thedistal end of the catheter 790. In use, the catheter 790 may be advancedthrough an airway and introduced through an extra-anatomic opening orport in an airway wall, into the lung tissue or parenchyma. The catheter790 may be introduced through a sheath 792 positioned through theextra-anatomic opening or port in the airway wall. The catheter 790 isadvanced into a target tumor and the anchors 791 or barbs or scoops atthe distal end of the catheter 790 are actuated or popped-out eitherbefore or after entry into the tumor. The catheter 790 is then pulled ordrawn back toward the extra-anatomic opening or port in the airway wall,with the anchors 791 or barbs capturing the tumor or samples of thetumor, pulling the tumor or tumor sample back toward the extra-anatomicopening or port, or through the extra-anatomic opening or port and intoor through the airway for removal. Optionally, the anchors or barbs maybe retracted or collapsed and the tumor, tumor sample or other tissuemay be pulled out or removed through the extra-anatomic opening or portand/or through the airway.

In another variation, a platform for accessing tumors or other tissue inthe lung through an extra-anatomic opening or port in the airway wall isprovided. Various forms of real time imaging may be utilized such as CT,MRI, PET, ultrasound, or fluoroscopy. A catheter, e.g., a 21 Ga needlesampling (TBNA) catheter, may be fed through a working channel of abronchoscope. A small needle size may minimize the risk of bleeding. Asteerable or non-steerable sheath (e.g., 2.0 mm to 3.0 mm OD) may be fedover the needle, but also within the scope working channel to providesteering and protection against seeding cancerous cells back into thenon-cancerous tissue as the needle is withdrawn from the tumor.Optionally, a Doppler probe may be fed through or next to the needlelumen and may be utilized to sense and/or avoid blood vessels.

Lung tumors may be located deep in the lung tissue where they mayrequire the winding or snaking of catheters through very tortuousairways or around various structures to access the tumor. When acatheter is fed deep enough in the airways to be as close as possible toa tumor, it may not be possible to articulate the catheter to point itdirectly at or in the direction of the tumor because the airway at thatpoint is very narrow.

Therefore, in certain variations, an access platform for accessingtarget tissues (e.g., diseased tissue, tumors, parenchyma or othertissues or structures) in a lung or other area of the body, through anopening, extra-anatomic opening or port through the airway wall isprovided. The target tissue or structures may be located outside of theairway in which the opening is created or beyond the airway wall, e.g.,in the parenchyma of the lung.

In one variation, an approach to access a target tissue (e.g., diseasedtissue, tumors, parenchyma or other tissues or structures) in the lungmay utilize a more “straight-line” or substantially straight path. Apath may be straight or substantially straight, allowing for some or noturns. Access to the central airways may be achieved by using a standardbronchoscope or other scope or elongate instrument. Instead of feedingthe bronchoscope deep into the smaller airways of the lungs wheremanipulation or articulation of the scope may be reduced or eliminated,a target site or point in a larger airway or central airway may bedetermined or selected, which may allow a straight, semi-straight orsubstantially straight tunnel, channel or path to be created leadingdirectly to the target tissue, parenchymal tissue or tumor. The targetsite or point on the airway wall may be located in an area of the airwaywhere a standard scope or access tool, e.g., one having a diameter fromabout 0-5 mm, may be articulated, manipulated or turned at variousdegrees, e.g., 90 degrees, such that within the airway the scope oraccess tool may be oriented to point or face in the direction of ordirectly at the target tissue in the lung, e.g., a tumor. From thistarget site on the airway wall, an elongate instrument or other tool maybe advanced through an opening in the airway wall to the target tissueor tumor in the lung in a substantially straight path or path thatminimizes or reduces the number of turns and twists required to reach oraccess the target tissue or tumor while traveling through theparenchymal or lung tissue.

The target site or point, which also may be called a point of entry orPOE, may be determined by taking into account or considering one or moreof the following factors: (1) the size of the airways; (2) the outerdiameter of a bronchoscope or other scope used to advance an elongateinstrument or other tool or instrument in the airway; (3) the amount ofroom or space available within the airway to articulate the scope sothat the scope working channel or elongate instrument can point towardsthe target tissue or tumor, (4) the position of blood vessels in thelung; (5) the location of pleural surfaces within the lung; (6) thelocation of other airways in the lung, and/or (7) the location, size,and shape of the target tissue or tumor. The POE location may becalculated by software algorithms or determined by visually assessingthe factors stated above. Software algorithms may also be utilized todetermine the direction or orientation of the tunnel, channel or pathfrom the POE to the target tissue in 3D space.

Once the POE and tunnel, channel or path direction or orientation isdetermined, a needle or other piercing member may be fed from theworking channel of the scope to make a hole through the airway wall atthe POE. This may be followed by a balloon catheter or mechanicaldilator to dilate the hole or opening. Alternatively, other means may beused to create a hole big enough to allow subsequent passing of otherlarger diameter tools. For example, a circular punch, a flat blade witha pointed tip, a cross shaped blade with a sharpened tip, an RF probe,or an RF snare may be used to create a slit, slits, or a larger openingin the airway wall without employing a dilation balloon. Once the holehas been dilated, a sheath or other elongate instrument may be fedthrough the hole or opening and into the lung tissue. The sheath maycontain a dissecting catheter which may fill the entire or substantiallyentire internal diameter of the sheath so that when the sheath is fedthrough lung tissue, matter does not accumulate inside the sheath. Thetip of the dissecting catheter may be sharp to tunnel through tissue orit may be rounded to allow it to tunnel without perforating bloodvessels or other structures. The rounded tip may easily push through theless dense parenchymal tissue, and simply push more dense vessels orother structures out of the way without damaging them. The tip maytunnel or advance through the lung tissue in substantially straight pathwhere turns are minimized or eliminated. Once the sheath and dissectingcatheter are fed to the target tissue or tumor, the dissecting cathetermay be removed, leaving the sheath in place to be used to access thetarget tissue or tumor for monitoring, diagnostic, or therapeuticprocedures or for the delivery of other tools to the target tissue toperform various procedures.

In the variations above, the order of introducing each of the devicesmay vary. For example, the needle and sheath may be fed through abronchoscope or scope or other delivery instrument simultaneously. Oncea needle is used to make the hole or opening in the airway wall, theneedle may be replaced by a balloon, and then a balloon may be replacedby a dissection catheter while the sheath remains in place. Variousfeatures of these devices may be combined into a single device, forexample, the balloon may be mounted to the outside diameter of theneedle.

In the variations above, various forms of real time imaging may be usedto guide the sheath to the target tissue or tumor. For example, CT, MRI,PET, ultrasound, fluoroscopy or electromagnetic fields may be used. Thesheath or other devices may be rendered radiopaque, or radiopaque marksmay be placed on the sheath or other devices to provide visibility whileutilizing these imaging modalities. Also visible marks may be placed onthe outside of the devices so that the physician using the devices maymeasure the depth that the devices are fed into the lung tissue bywatching the marks as they are fed into the hole in the airway wall.

In the variations above, steerability may be designed into any or all ofthe devices. For example, the sheath may be made steerable by includingoff-center-axis pull wires to allow the tip or distal end to be steeredin one or multiple planes.

In the variations above, various methods may be used to avoidperforating blood vessels. Catheter, sheath or other elongate instrumentmounted transducers may be used to listen for blood using the Dopplerprinciple or ultrasound imaging may be employed. These methods may befed through the channel of a piercing member or needle, or through theelongate instrument or sheath prior to introduction of the piercingmember or needle. Alternatively, the methods or devices for avoiding ordetecting blood vessels may be fed next to the piercing member or needleor be incorporated into one or more of the other elongate instruments ordevices described.

In an alternative variation, the elongate instrument or sheath deviceand/or method described above may be used in therapeutic procedures. Forexample, an RF snare catheter may be fed through the sheath, where thesheath prevents cancerous cells from being seeded into healthy tissue asthey are removed with the RF snare catheter. In another variation, acatheter having a rotating morcellating tip may be fed through thesheath and used to remove the tumor through the sheath. The sheathprevents cancerous cells from being seeded into healthy tissue as theyare removed. The access sheath may also be used to introduce a needle orblunt catheter for injecting agents, e.g. chemotherapy drugs, directlyinto or the tumor or infusing the local space around the tumor withthese agents. The access sheath may also be used to introduce aradioactive substance, e.g. seed, fluid, etc. directly into the tumor orinfusing/implanting the local space around the tumor with thesesubstances.

Additional diagnostic procedures that may be performed through anextra-anatomic opening or port through an airway wall include (1)injecting dye which is taken up by tumors (e.g., a radioactive dyelinked to an antibody) to visualize and locate a tumor, (2) injecting aphotodynamic therapy agent (PDT) directly into a tumor and illuminatingthe tumor with an LED mounted on a catheter, positioned in closeproximity to the tumor to visualize the tumor, (3) implanting a deviceor beacon or tracking device or RFID into a tumor or target tissue thatdetects changes in the tumor or tissue growth or properties and reportsback such that tumor or tissue may be monitored or tracked over time.

In certain variations, brachytherapy may be performed or a radiationseed may be placed through an extra-anatomic opening or port in anairway wall and positioned in lung tissue, parenchyma, or other tissue.For example, a small radiation or energy capsule may be advanced throughan extra-anatomic opening or port in an airway wall and into or next toa target tumor, lung tissue, or parenchyma where the capsule may beactivated to release energy or radiation. The capsule may be activatedchemically, electronically, or may be activated from the outside withenergy, causing the capsule to release local energy to treat a targettissue or tumor. In certain variations, focused energy may be deliveredto the capsule, magnifying the release of energy from the capsule totreat target tissue. Optionally, a regimen may be utilized where thedelivery of energy causes the release of different forms of energy ortherapeutics locally to a target tissue at varying times orsimultaneously and/or in different amounts.

In another variation, methods and device are provided for treating lungtumors performed through an extra-anatomic opening or port through anairway wall. A coil or electrodes from a coil or another device whichcan generate an alternating current is implanted into the tumor andexcited or activated by an external electromagnetic or magnetic field.The coil or other device delivers energy into the tumor and heats orablates the blood vessels supplying blood to the tumor. A repetitivelocalized heating of the tumor may be provided. The coil may be excitedperiodically, e.g., every few days, and eventually the tumor may bekilled as the blood vessels are destroyed and can no long supply bloodto the tumor. Microwaves or a lower frequency, e.g., 30-60 hertz may beused to destroy the tumor blood vessels. The device and method may allowfor repetitive localized heating of a tumor. The procedure may take afew seconds and may cause minimal to no pain.

In another variation, immunotherapy may be performed through anextra-anatomic opening or port in an airway wall where an immuneresponse is stimulated by activating tumor tissue with RF or anotherenergy source. The immune system will then be activated and destroy anyremaining tumor cells. The body becomes immunized against that tumorcell wherever else it may reside in the body.

In another variation, a capsule with a chemotherapy drug may bepositioned at a target tissue and a magnetic or electromagnetic fieldmay be applied which causes the capsule to release a desired amount ofthe drug. In another variation, an implantable drug pump, e.g., fordelivering a chemotherapy drug, or an implantable stimulation device fordelivering a stimulating or destructive current to a target tissue ortumor may be advanced through an extra-anatomic opening or port in anairway wall and implanted in tissue or parenchyma. The stimulationdevice may be powered by varying sources, e.g., battery powered orpowered by an external power source or electromagnetic or magneticfield. Optionally, the stimulation device may deliver RF, laser, oranother energy source to the target tissue or tumor.

In another variation, a method and a device for performing apleurocentesis are provided. The pleurocentesis may be performed byentering the lung through an extra-anatomic opening or port in an airwaywall. A drainage channel 810 may be created to drain fluid from thepleural space. As illustrated in FIG. 25A, the drainage channel 810 maybe created by advancing a catheter or tube into the periphery airwaysand through an extra-anatomic opening or port in an airway wall, wherethe opening or port is positioned in close proximity to a fissure. Thecatheter or tube is advanced into the fissure and fluid in the pleuralspace may be suctioned or drained out via the catheter or tube.

Alternatively, as illustrated in FIG. 25B, instead of sucking fluid fromthe pleural space, a first end of a catheter or tube may be insertedinto a fissure and a second end of the catheter or tube may be insertedinto the venous or lymphatic system to create a bypass drainage channel812, directing or draining the fluid from the pleural space into thevenous or lymphatic system. The bypass drainage channel prevents fluidcollection in the pleural space, allowing the fluid to automaticallydrain. This device and method may be useful for treating conditionswhere the recurring build up of fluid in the pleural space is common,e.g., in patients suffering from lung cancer.

In other variations, various devices and methods are provided fortreating pulmonary hypertension through an extra-anatomic opening orport in an airway wall. In one variation, a vasodilator, e.g., Viagra®,may be delivered to the lung to cause vasodilatation and reducepulmonary hypertension. In another variation, a fistula or shunt may bepositioned between a vein and artery inside the lung, eitherperipherally or centrally. The fistula provides a bypass between theartery and vein, which reduces resistance to blood flow through theartery and thereby reduces pressure in the artery. The artery and veinare positioned next to each other and a connector or shunt may be usedto connect the vein and artery. In another variation, blood may beperpetually shunted from an artery to a vein according to the approachused by Rox Medical as follows: The ROX CO2UPLER™ device, a smallmetallic stent-like implant, couples two blood vessels together in thepelvic region. The implant creates a fistula, a calibrated passage,between the artery and vein, which allows a calculated amount ofoxygen-rich blood to be rerouted from the artery to the vein, returningback to the heart and lungs for further increased oxygen saturation. TheROX FLO2W™ Procedure is a percutaneous interventional approach intendedfor treatment of patients with COPD.

Optionally, the above methods may be utilized for diagnosis. Forexample, while in the artery, blood pressure may be measured directly.Also, Doppler may be utilized to determine the distension range of anartery.

In other variations, devices and methods are provided for diagnosing,monitoring, or treating diabetes via an extra-anatomic opening or portin an airway wall. A device and method for performing noninvasiveglucose monitoring may include an implantable glucose sensorpositionable on an airway. A sensor may be positioned on the inside ofthe airway wall or the sensor may be advanced through an extra-anatomicopening or port in the airway wall and attached, anchored or clamped tothe outside airway wall next to a vessel, e.g., a pulmonary artery orcapillary. A sensor may be placed anywhere along the airway (inside oroutside) in proximity to capillaries, arteries, blood vessels or otherblood supply. The glucose levels may be detected and the sensor maysend, transmit, or broadcast a signal to an external device, e.g., acell phone, to collect and/or analyze the glucose related data. Theglucose reading may be performed at preset time intervals or in responseto an event, e.g., a skin prick or after food consumption. Optionally,an external energy source, e.g., a coil, may be coupled to a sensor orother internal device to supply energy so the sensor or internal devicedoesn't need its own energy source.

In other variations, a variety of sensors for taking variousmeasurements by be utilized through extra-anatomic ports in the airwaywall. For example, a sensor for measuring lactate levels, to detectinfection or early warning indicators for pneumonia, or otherrespiratory problems may be utilized.

Pulmonary arterial hypertension may result from the proliferation andthickening of smooth muscle in the pulmonary artery, which may reducethe diameter of the arterial lumen and increase the pressure of theblood flow through the lumen. In another variation, an RF catheter maybe advanced through an extra-anatomic opening or port in the airwaywall, to a pulmonary artery. The RF catheter may be introduced into apulmonary artery to reduce smooth muscle in the pulmonary artery, tothereby increase the diameter of the artery lumen and treat pulmonaryhypertension. The RF catheter may be used to treat the smooth muscle,eliminating smooth muscle which is replaced with fibrotic cells. Use ofthe RF catheter on narrow segments of the pulmonary artery may increasethe luminal area in the artery or vessel and decrease the pressure ofarterial flow. The RF catheter may include electrodes in an angioplastystyle balloon to treat the arterial or vascular wall. This may reducethe creation of thrombosis that could result from direct contact betweenthe electrode and the blood. The configuration of the electrode(s) onthe RF catheter may be monopolar, bi-polar and may include a variety ofarray designs (baskets, mesh, electrode pairs, point electrodes, etc.).

In another variation, a device and method for stimulating a diaphragm orrespiration is provided. The device may include an implantable pulsegenerator or pacer having leads or electrodes. The device is advancedthrough an extra-anatomic opening or port in the airway wall andimplanted in the lung. The device includes CO2 sensors, such that thedevice stimulates breathing in response to detected CO2 levels. Thisdevice may be used in patients suffering from emphysema, increasing thepatient's respiratory effort when their CO2 levels start to rise. Thedevice may also be used in patients who have suffered spinal cordinjuries, paralysis, or who have MS, or other conditions where thepatient requires a stimulated increase in respiration.

In another variation, a device and method for treating patient's havingesophageal motility issues, where their esophagus doesn't squeeze orconstrict properly causing food to get lodged in the esophagus, isprovided. For example, a method for treating esophageal motilityproblems includes performing electronic pacing or stimulation of theesophagus through an extra-anatomic opening or port in the airway walland through the pleura of the lung, which sits in proximity to or alongthe esophagus.

In another variation, a lapband or other restrictive device may beadvanced through an extra-anatomic opening or port in the airway walland through the lung or through the trachea, and positioned around theesophagus to constrain the esophagus and restrict the rate at which foodmay pass through the esophagus. Such a device may assist in thetreatment of obesity or other conditions related to obesity.

In another variation, methods and devices are provided for facilitatingimproved VQ (V=perfusion; Q=ventilation) matching. Blood vessels may beaccessed via an extra-anatomic opening or port through an airway wall.The blood vessels that are feeding areas of the lung that are poorlyventilated may be partially or completely closed off, redirecting bloodto areas of the lung that are better ventilated. As a result, lungefficiency and overall perfusion/ventilation may be improved. In certainvariations, blood vessels may be cauterized, closing off the bloodvessel. In other variations, a wire, e.g., a nitinol wire, may be usedto close off a blood vessel. Optionally, a U loop may be advancedthrough a first extra-anatomic opening or port in the airway wall,around a blood vessel, and back into the air way though the first or asecond extra-anatomic opening or port in the airway wall. The U loop iscinched down, closing off or partially closing off the blood vessel.

In another variation for applying a therapeutic treatment via anextra-anatomic opening or port in an airway wall, a drug deliverycapsule, pump, patch, or sponge may be advanced through the opening orport and implanted into parenchyma or other tissue. The capsule, etc.may deliver drugs over a period of time and may include a refillable orreloadable reservoir.

FIG. 26 illustrates a variation of a pacing device which may be advancedthrough an extra-anatomic opening or port through the airway wall. Thedevice may be in the form of a leadless pacemaker 730 or defibrillatingdevice. The leadless pacemaker may use the pacemaker metal case or canas a first lead and the pleura, which rests against or in closeproximity to the heart, as a second lead. FIG. 26 shows a firstelectrode 731 placed on the metal case or can and a second electrode 732placed on the pleura. In use, the pacemaker 730 may be advanced throughan extra-anatomic opening or port in an airway wall and positioned inthe lung to provide stimulation through the pleura, into the heart.

A variety of other procedures may be performed through an extra-anatomicopening or port or channel through an airway wall including for example:In one variation, a catheter may generate ultrasound and an image may beobtained from behind the catheter or tumor to localize a tumor. Inanother variation, markers could be placed on a periphery of a tumor ornodule and the volume of the nodules may be detected based on the factthat if the tumor or nodule is growing, the markers will separate fromone another. In another variation, a sensor may be positioned outside ofthe body and catheter on the inside of the body that generates x-rays,ultrasound, light or other modality which provides a shadow of a mass,which you can then use to localize the mass. The generating catheter maybe moved closer and closer to the tumor to localize the mass byobserving how the shadow moves. In another variation two catheters maybe positioned in two different areas of the lung. One catheter may shinelight toward the other such that the size of the shadow cast by thelight emitting catheter on the other catheter may be seen. This wouldprovide a way to track size or locate a target tissue, mass or object.In certain variations, a tumor may be encapsulated or frozen bycryogenic procedures. In certain variations, blood vessels feeding atumor or other tissue may be located and ablated, e.g., using hot biopsyforceps or a cauterizing knife or other ablation tool. Feeding vesselsto a heterogeneous lobe may be ablated. In certain variations, a ziptieor gastro-type band may be positioned around a nodule or a vesselleading to a poorly ventilated area of the lung.

In any of the variations described therein, elongate instrument mayrefer to a catheter, sheath, scope, bronchoscope piercing member or anyother medical device for insertion into the body. Optionally, any of theprocedures described herein may be performed during or after thecreation of a channel, opening, extra-anatomic opening or port throughan airway wall.

In certain variations, a method of accessing target tissue in a lung isprovided which includes locating a target site on an airway wall,wherein the target site is in a location that allows for creation of anopening leading to the target tissue and for advancement of an elongateinstrument through the opening to the target tissue. The opening may bemade through the airway wall at the target site. The target tissue maybe located outside of the airway or beyond the airway wall through whichthe opening is made. The target site may be in a location that allowsfor advancement of an elongate instrument to the target tissue along asubstantially straight path. The target site may be in a location thatallows for advancement of an elongate instrument from the opening in theairway wall to the target tissue along a substantially straight path.

In certain variations, the target site may be determined or selected byconsidering one or more of the following factors: a size of the airway;an outer diameter of a scope used to advance the elongate instrument inthe airway; space available within the airway to articulate a scope sothat the scope working channel can point towards the target tissue; aposition of blood vessels in the lung; a location of pleural surfaceswithin the lung; a location of other airways in the lung; and/or alocation, size, and/or shape of a target tissue. The target site may bein a location that allows for the creation of a substantially straighttunnel or channel leading from the target site or opening to the targettissue. Locating a target site on the airway wall may includedetermining a direction or orientation of a tunnel or channel in space,the tunnel or channel leading from the airway wall to the target tissuein a substantially straight line or path.

In certain variations, a method of accessing target tissue in a lung mayinclude: advancing an elongate instrument to a target site in an airwayof the lung; creating an opening through the airway wall at the targetsite, where the opening leads to the target tissue; and advancing theelongate instrument through the opening to the target tissue. Theelongate instrument may be advanced to the target tissue along asubstantially straight path. The elongate instrument may be advancedfrom the opening in the airway wall to the target tissue along asubstantially straight path. A method of accessing target tissue in alung may include: locating a target site on an airway wall, wherein thetarget site is in a location that allows for creation of an openingthrough the airway wall, that leads to the target tissue, and foradvancement of the elongate instrument through the opening to the targettissue. The elongate instrument may be advanced to the target tissuealong a substantially straight path.

In certain variations a method of accessing target tissue may includeone or more of the following: creating an opening through the airwaywall at the target site by advancing a piercing member to the targetsite and through the airway wall; dilating the opening with a ballooncatheter or other expandable device; advancing an elongate instrumentthrough the opening to the target tissue; articulating the elongateinstrument within the airway such that a distal end of the elongateinstrument points in a direction facing the target tissue before theelongate instrument advances through the opening; advancing a dissectingcatheter having a sharp or rounded tip positioned within the elongateinstrument through the opening and to the target tissue; leaving theelongate instrument in place to provide access to the target tissue forperforming monitoring, diagnostic or therapeutic procedures or fordelivering instruments or tools to the target tissue; performing imagingto guide the elongate instrument to the target tissue. The imagingmethod used may be comprised of at least one of: fluoroscopy, computedtomography, positron emission technology, magnetic resonance imaging, orultrasound. The target tissue may be a tumor or diseased tissue.

In certain variations, a method of accessing target tissue in a lung mayinclude selecting or locating a target site in an airway of the lungwherein the target site is in a location that allows for creation of anopening through the airway wall, the opening leading to the targettissue, and/or wherein the target site is in a location that allows foradvancement of an elongate instrument through the opening to the targettissue along a substantially straight path; advancing an elongateinstrument to a target site in an airway of the lung; creating anopening through the airway wall at the target site, the opening leadingto the target tissue; advancing the elongate instrument and a blunttipped dissecting catheter positioned within the elongate instrumentthrough the opening and to the target tissue; leaving the elongateinstrument in place to provide access to the target tissue forperforming monitoring, diagnostic or therapeutic procedures.

In certain variations a system for accessing target tissue in a lung mayinclude: a piercing member configured to create an opening through anairway wall at a target site on the airway wall, the opening leading tothe target tissue; a dissecting catheter configured for advancementthrough the opening and for creating a channel through the lung to thetarget tissue; and an elongate instrument configured for advancementthrough the opening and the channel to the target tissue, wherein theelongate instrument is configured to provide access to the target tissuefor performing monitoring, diagnostic or therapeutic procedures.

In certain variations, a method of navigating an elongate instrumentthrough an opening in an airway wall to target tissue in the lung mayinclude advancing an elongate instrument within an airway of the lung;advancing the elongate instrument through an opening in the airway wall;and providing an electromagnetic sensor to guide or track the elongateinstrument.

In certain variations a method of accessing target tissue in a lung, mayinclude locating a target site on an airway wall, wherein the targetsite is in a location that allows for creation of an opening leading tothe target tissue and for advancement of an elongate instrument throughthe opening to the target tissue; and providing an electromagneticsensor to guide or track the elongate instrument.

In certain variations the methods may also include applying anelectromagnetic field in a vicinity of the electromagnetic sensor toguide or track the elongate instrument. The electromagnetic field may beregistered to a 3D model of the lung which has been reconstructed from aset of radiographic images and the radiographic images may be from a CTscan. The electromagnetic sensor may be positioned at a distal end ofthe elongate instrument. The target site may be in a location thatallows for advancement of an elongate instrument to the target tissuealong a substantially straight path. The target site may be in alocation that allows for advancement of an elongate instrument from theopening in the airway wall to the target tissue along a substantiallystraight path.

In certain variations the target site may be determined or selected byconsidering one or more of the following factors: a size of the airway;an outer diameter of a scope used to advance the elongate instrument inthe airway; space available within the airway to articulate a scope sothat the scope working channel can point towards the target tissue; aposition of blood vessels in the lung; a location of pleural surfaceswithin the lung; a location of other airways in the lung; and/or alocation, size, and/or shape of a target tissue. The target site may bein a location that allows for the creation of a substantially straighttunnel or channel leading from the target site or opening to the targettissue. Locating a target site on the airway wall may includedetermining a direction or orientation of a tunnel or channel in space,the tunnel or channel leading from the airway wall to the target tissuein a substantially straight line or path.

In certain variations a method of accessing target tissue may includeone or more of the following: creating an opening through the airwaywall at the target site by advancing a piercing member to the targetsite and through the airway wall; dilating the opening with a ballooncatheter or other expandable device; advancing an elongate instrumentthrough the opening to the target tissue; articulating the elongateinstrument within the airway such that a distal end of the elongateinstrument points in a direction facing the target tissue before theelongate instrument advances through the opening; advancing a dissectingcatheter having a sharp or rounded tip positioned within the elongateinstrument through the opening and to the target tissue; leaving theelongate instrument in place to provide access to the target tissue forperforming monitoring, diagnostic or therapeutic procedures or fordelivering instruments or tools to the target tissue; performing imagingto guide the elongate instrument to the target tissue. The imagingmethod used may be comprised of at least one of: fluoroscopy, computedtomography, positron emission technology, magnetic resonance imaging, orultrasound. The target tissue may be a tumor or diseased tissue. Themethod may include guiding the elongate instrument or a dissectingcatheter with the electromagnetic sensor or an electromagnetic field.

In certain variations a method of accessing target tissue in a lung mayinclude: advancing an elongate instrument to a target site in an airwayof the lung; creating an opening through the airway wall at the targetsite, the opening leading to the target tissue; advancing the elongateinstrument through the opening to the target tissue; and guiding theelongate instrument with an electromagnetic sensor or an electromagneticfield. The elongate instrument may be advanced to the target tissuealong a substantially straight path. The elongate instrument may beadvanced from the opening in the airway wall to the target tissue alonga substantially straight path.

In certain variations the method may include locating a target site onan airway wall, wherein the target site is in a location that allows forcreation of an opening leading to the target tissue and for advancementof the elongate instrument through the opening to the target tissue.

In certain variations a method of accessing target tissue in a lung mayinclude: selecting a target site in an airway of the lung wherein thetarget site is in a location that allows for creation of an openingthrough the airway wall, the opening leading to the target tissue, andwherein the target site is in a location that allows for advancement ofan elongate instrument through the opening to the target tissue along asubstantially straight path; advancing an elongate instrument to atarget site in an airway of the lung; creating an opening through theairway wall at the target site, the opening leading to the targettissue; advancing the elongate instrument and a blunt tipped dissectingcatheter positioned within the elongate instrument through the openingand to the target tissue; guiding the elongate instrument and dissectingcatheter with an electromagnetic sensor or an electromagnetic field; andleaving the elongate instrument in place to provide access to the targettissue for performing monitoring, diagnostic or therapeutic procedures.

In certain variations a system for accessing target tissue in a lung mayinclude: a piercing member configured to create an opening through anairway wall at a target site on the airway wall, the opening leading tothe target tissue; a dissecting catheter configured for advancementthrough the opening and for creating a channel through the lung to thetarget tissue; and an elongate instrument configured for advancementthrough the opening and the channel to the target tissue, wherein theelongate instrument is configured to provide access to the target tissuefor performing monitoring, diagnostic or therapeutic procedures; and aguiding system for guiding the elongate instrument and dissectingcatheter with an electromagnetic sensor or an electromagnetic field.

All publications, patent applications, patents, and other referencesmentioned herein are incorporated by reference in their entirety. To theextent there is a conflict in a meaning of a term, or otherwise, thepresent application will control. Although variations of the foregoinginvention has been described in some detail by way of illustration andexample for purposes of clarity of understanding, it will be readilyapparent to those of ordinary skill in the art in light of the teachingsof this invention that certain changes and modifications may be madethereto without departing from the spirit or scope of the appendedclaims. It is also contemplated that combinations of the above describedembodiments/variations or combinations of the specific aspects of theabove described embodiments/variations are within the scope of thisdisclosure.

Each of the individual variations described and illustrated herein hasdiscrete components and features which may be readily separated from orcombined with the features of any of the other variations. Modificationsmay be made to adapt a particular situation, material, composition ofmatter, process, process act(s) or step(s) to the objective(s), spiritor scope of the present invention.

Methods recited herein may be carried out in any order of the recitedevents which is logically possible, as well as the recited order ofevents. Furthermore, where a range of values is provided, everyintervening value between the upper and lower limit of that range andany other stated or intervening value in that stated range isencompassed within the invention. Also, any optional feature of theinventive variations described may be set forth and claimedindependently, or in combination with any one or more of the featuresdescribed herein.

All existing subject matter mentioned herein (e.g., publications,patents, patent applications and hardware) is incorporated by referenceherein in its entirety except insofar as the subject matter may conflictwith that of the present invention (in which case what is present hereinshall prevail). The referenced items are provided solely for theirdisclosure prior to the filing date of the present application. Nothingherein is to be construed as an admission that the present invention isnot entitled to antedate such material by virtue of prior invention.

Reference to a singular item, includes the possibility that there areplural of the same items present. More specifically, as used herein andin the appended claims, the singular forms “a,” “an,” “said” and “the”include plural referents unless the context clearly dictates otherwise.It is further noted that the claims may be drafted to exclude anyoptional element. As such, this statement is intended to serve asantecedent basis for use of such exclusive terminology as “solely,”“only” and the like in connection with the recitation of claim elements,or use of a “negative” limitation. Unless defined otherwise, alltechnical and scientific terms used herein have the same meaning ascommonly understood by one of ordinary skill in the art to which thisinvention belongs.

This disclosure is not intended to be limited to the scope of theparticular forms set forth, but is intended to cover alternatives,modifications, and equivalents of the variations described herein.Further, the scope of the disclosure fully encompasses other variationsthat may become obvious to those skilled in the art in view of thisdisclosure. The scope of the present invention is limited only by theappended claims.

We claim:
 1. A method of accessing and treating a target tissue in alung, the method comprising: creating an opening through the airway wallat the target site with a hole-making instrument, the opening leading tothe target tissue; tunneling from the opening in the airway wall to thetarget tissue by advancing an elongate instrument and a dissectorpositioned therein from the opening to the target tissue; removing thedissector from the elongate instrument such that the elongate instrumentdefines an access channel to the target tissue; and treating the targettissue through the access channel defined by the previously positionedelongate instrument leading to the target tissue.
 2. The method of claim1, wherein the step of treating comprises removing the target tissue. 3.The method of claim 2, wherein the removing is carried out by snaringthe target tissue with a tissue-snare catheter.
 4. The method of claim2, wherein the removing is carried out by morcellating the target tissuewith a morcellating-tip catheter.
 5. The method of claim 1, wherein thestep of treating comprises ablating the target tissue with anenergy-delivering catheter.
 6. The method of claim 1, wherein the stepof treating comprises destroying the target tissue.
 7. The method ofclaim 6, wherein the destroying comprises injecting an agent into thetarget tissue.
 8. The method of claim 7, wherein the agent comprises atleast one of a chemotherapy drug and a radioactive substance.
 9. Themethod of claim 6, wherein the destroying comprises advancing an implantinto the target tissue.
 10. The method of claim 9, wherein the implantis one selected from the group consisting of a capsule, coil, andelectrode.
 11. The method of claim 10, wherein the implant is a capsule,and the capsule is configured to release radiation.
 12. The method ofclaim 11, wherein the capsule is activated by a mechanism selected fromthe group consisting of chemical and electronic mechanisms.
 13. Themethod of claim 12, wherein the capsule is activated electronically froman energy source outside the body.
 14. The method of claim 9, whereinthe implant is an electrode and configured to deliver alternatingcurrent to the tumor.
 15. The method of claim 14, wherein the electrodeis activated from an external source selected from the group consistingof an electromagnetic and magnetic field.
 16. The method of claim 14,wherein the electrode is excited repeatedly.
 17. The method of claim 1,further comprising dilating the opening with a balloon catheter; andperforming imaging to guide the elongate instrument to the targettissue.
 18. The method of claim 1, wherein the target tissue is a tumor.19. The method of claim 1, further comprising locating the target siteon the airway wall, wherein the target site is in a location that allowsfor creation of the opening leading to the target tissue and foradvancement of the elongate instrument through the opening to the targettissue along a substantially straight path.
 20. The method of claim 1,further comprising articulating the elongate instrument.